Science.gov

Sample records for confounding effect modification

  1. Assessing confounding, effect modification, and thresholds in the association between ambient particles and daily deaths.

    PubMed Central

    Schwartz, J

    2000-01-01

    I examined the relationship between daily deaths and airborne particles in 10 U.S. cities with varying climatic conditions and seasons in which particle concentrations were high. Airborne particles were associated with significant increases in daily deaths [0.67% increase for a 10 microg/m(3) increase in particles; 95% confidence interval (CI), 0.52-0.81%]. This association was the same in summer and winter. To examine potential confounding by other pollutants, I regressed city- and season-specific effect sizes against the relationship between airborne particles and other pollutants. Controlling for other pollutants did not substantially (or significantly) change the estimated effect of airborne particles. Socioeconomic differences between cities likewise did not modify the effect. The increase in daily deaths that occurred out of hospitals (0.89% per 10 microg/m(3); CI, 0.67-1.10%) was substantially greater than the increase in deaths in hospitals (0. 49%; CI, 0.31-0.68%). This is consistent with results previously reported in Philadelphia, Pennsylvania, and suggests that the particle-associated deaths are not just being brought forward by a few days. It is also consistent with recent animal and human studies of the mechanisms of particle toxicity. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:10856032

  2. Cord Blood Methylmercury and Fetal Growth Outcomes in Baltimore Newborns: Potential Confounding and Effect Modification by Omega-3 Fatty Acids, Selenium, and Sex

    PubMed Central

    Wells, Ellen M.; Herbstman, Julie B.; Lin, Yu Hong; Jarrett, Jeffery; Verdon, Carl P.; Ward, Cynthia; Caldwell, Kathleen L.; Hibbeln, Joseph R.; Witter, Frank R.; Halden, Rolf U.; Goldman, Lynn R.

    2015-01-01

    evidence for interaction between MeHg and n-3 HUFAs; infants with higher MeHg and n-3 HUFAs had lower birth length and head circumference. These results should be verified with additional studies. Citation Wells EM, Herbstman JB, Lin YH, Jarrett J, Verdon CP, Ward C, Caldwell KL, Hibbeln JR, Witter FR, Halden RU, Goldman LR. 2016. Cord blood methylmercury and fetal growth outcomes in Baltimore newborns: potential confounding and effect modification by omega-3 fatty acids, selenium, and sex. Environ Health Perspect 124:373–379; http://dx.doi.org/10.1289/ehp.1408596 PMID:26115160

  3. Confounding in the Estimation of Mediation Effects.

    PubMed

    Li, Yan; Bienias, Julia L; Bennett, David A

    2007-03-01

    A mediation effect explains the relationship of a risk factor and an outcome through a mediator variable which is a step in their pathway. Under the assumption of no cycling in the causal relationship, we consider various situations in which a fourth variable may interfere the estimation of a mediation effect as a confounding factor. Our asymptotic results, which are supported by a Monte Carlo study, show that adjusting for confounding factors under certain conditions might lead to biased estimates. A general guideline is provided for when it is appropriate to adjust for confounding factors in estimating a mediation effect. We apply the guideline to the estimation of the mediation effect of Alzheimer's disease pathology in the relationship between the Apolipoprotein E ε4 allele and cognitive function among 125 deceased participants from the Religious Orders Study, a longitudinal, clinical-pathologic study of aging and Alzheimer's disease. PMID:17940582

  4. Confounding in the Estimation of Mediation Effects

    PubMed Central

    Li, Yan; Bienias, Julia L.; Bennett, David A.

    2007-01-01

    Summary A mediation effect explains the relationship of a risk factor and an outcome through a mediator variable which is a step in their pathway. Under the assumption of no cycling in the causal relationship, we consider various situations in which a fourth variable may interfere the estimation of a mediation effect as a confounding factor. Our asymptotic results, which are supported by a Monte Carlo study, show that adjusting for confounding factors under certain conditions might lead to biased estimates. A general guideline is provided for when it is appropriate to adjust for confounding factors in estimating a mediation effect. We apply the guideline to the estimation of the mediation effect of Alzheimer’s disease pathology in the relationship between the Apolipoprotein E ε4 allele and cognitive function among 125 deceased participants from the Religious Orders Study, a longitudinal, clinical-pathologic study of aging and Alzheimer’s disease. PMID:17940582

  5. Confounding Effect in Clinical Research of Otolaryngology and Its Control.

    PubMed

    Yu, Yong-qiang; Huang, Dong-yan; Armijo Olivo, Susan; Yang, Huai-an; Bambanini, Yagesh; Sonnenberg, Lyn; Clark, Brenda; Constantinescu, Gabriela; Qian Yu, Jason; Zhang, Ming

    2015-06-01

    Confounding effect is a critical issue in clinical research of otolaryngology because it can distort the research's conclusion. In this review, we introduce the definition of confounding effect, the methods of verifying and controlling the effect. Confounding effect can be prevented by research's design, and adjusted by data analysis. Clinicians would be aware and cautious about confounding effect in their research. They would be able to set up a research's design in which appropriate methods have been applied to prevent this effect.They would know how to adjust confounding effect after data collection. It is important to remember that sometimes it is impossible to eliminate confounding effect completely, and statistical method is not a master key. Solid research knowledge and critical thinking of our brain are the most important in controlling confounding effect. PMID:26149004

  6. Determinants of congruency sequence effects without learning and memory confounds.

    PubMed

    Weissman, Daniel H; Jiang, Jiefeng; Egner, Tobias

    2014-10-01

    A common finding in distracter interference (e.g., Flanker) tasks is that the difference in mean reaction time (RT) between incongruent and congruent trials-the congruency effect-is smaller when the previous trial was incongruent relative to congruent. Over the past 2 decades, 2 main accounts of this congruency sequence effect (CSE) have been proposed. One posits that the CSE indexes trial-by-trial adjustments of cognitive control, which are triggered by expectation, response conflict, negative affect, or response suppression. The other holds that the CSE indexes feature integration and/or contingency learning processes that are confounded with congruency sequence in most studies. In 3 online experiments involving over 450 participants, we observed CSEs without such confounds when 2 preconditions were met: (a) stimulus-response translation could be completed more rapidly for the distracter than for the target and (b) the distracter and target appeared at the same location. We also found that CSE magnitude did not vary consistently with the size of the congruency effect. These findings reveal that CSEs can be observed in the absence of feature integration and contingency learning confounds, but impose important new constraints on certain cognitive control accounts of this phenomenon. PMID:25089574

  7. Confounding effects of indirect connections on causality estimation.

    PubMed

    Vakorin, Vasily A; Krakovska, Olga A; McIntosh, Anthony R

    2009-10-30

    Addressing the issue of effective connectivity, this study focuses on effects of indirect connections on inferring stable causal relations: partial transfer entropy. We introduce a Granger causality measure based on a multivariate version of transfer entropy. The statistic takes into account the influence of the rest of the network (environment) on observed coupling between two given nodes. This formalism allows us to quantify, for a specific pathway, the total amount of indirect coupling mediated by the environment. We show that partial transfer entropy is a more sensitive technique to identify robust causal relations than its bivariate equivalent. In addition, we demonstrate the confounding effects of the variation in indirect coupling on the detectability of robust causal links. Finally, we consider the problem of model misspecification and its effect on the robustness of the observed connectivity patterns, showing that misspecifying the model may be an issue even for model-free information-theoretic approach. PMID:19628006

  8. The Problem of Confounding in Studies of the Effect of Maternal Drug Use on Pregnancy Outcome

    PubMed Central

    Källén, Bengt

    2012-01-01

    In most epidemilogical studies, the problem of confounding adds to the uncertainty in conclusions drawn. This is also true for studies on the effect of maternal drug use on birth defect risks. This paper describes various types of such confounders and discusses methods to identify and adjust for them. Such confounders can be found in maternal characteristics like age, parity, smoking, use of alcohol, and body mass index, subfertility, and previous pregnancies including previous birth of a malformed child, socioeconomy, race/ethnicity, or country of birth. Confounding by concomitant maternal drug use may occur. A geographical or seasonal confounding can exist. In rare instances, infant sex and multiple birth can appear as confounders. The most difficult problem to solve is often confounding by indication. The problem of confounding is less important for congenital malformations than for many other pregnancy outcomes. PMID:22190949

  9. Does exposure prediction bias health effect estimation? The relationship between confounding adjustment and exposure prediction

    PubMed Central

    Dominici, Francesca

    2014-01-01

    In environmental epidemiology, we are often faced with two challenges. First, an exposure prediction model is needed to estimate the exposure to an agent of interest, ideally at the individual level. Second, when estimating the health-effect associated with the exposure, confounding adjustment is needed in the health-effects regression model. The current literature addresses these two challenges separately. That is, methods that account for measurement error in the predicted exposure often fail to acknowledge the possibility of confounding, while methods designed to control confounding often fail to acknowledge that the exposure has been predicted. In this paper, we consider exposure prediction and confounding adjustment in a health-effects regression model simultaneously. By using theoretical arguments and simulation studies, we show that the bias of a health-effect estimate is influenced by the exposure prediction model, the type of confounding adjustment used in the health-effects regression model, and the relationship between these two. Moreover, we argue that even with a health-effects regression model that properly adjusts for confounding, the use of a predicted exposure can bias the health-effect estimate unless all confounders included in the health-effects regression model are also included in the exposure prediction model. While these results of this paper were motivated by studies of environmental contaminants, they apply more broadly to any context where an exposure needs to be predicted. PMID:24815302

  10. Unobserved time effects confound the identification of climate change impacts.

    PubMed

    Auffhammer, Maximilian; Vincent, Jeffrey R

    2012-07-24

    A recent study by Feng et al. [Feng S, Krueger A, Oppenheimer M (2010) Proc Natl Acad Sci USA 107:14257-14262] in PNAS reported statistical evidence of a weather-driven causal effect of crop yields on human migration from Mexico to the United States. We show that this conclusion is based on a different statistical model than the one stated in the paper. When we correct for this mistake, there is no evidence of a causal link. PMID:22783021

  11. Confounding Effects of Phase Delays on Causality Estimation

    PubMed Central

    Vakorin, Vasily A.; Mišić, Bratislav; Krakovska, Olga; Bezgin, Gleb; McIntosh, Anthony R.

    2013-01-01

    Linear and non-linear techniques for inferring causal relations between the brain signals representing the underlying neuronal systems have become a powerful tool to extract the connectivity patterns in the brain. Typically these tools employ the idea of Granger causality, which is ultimately based on the temporal precedence between the signals. At the same time, phase synchronization between coupled neural ensembles is considered a mechanism implemented in the brain to integrate relevant neuronal ensembles to perform a cognitive or perceptual task. Phase synchronization can be studied by analyzing the effects of phase-locking between the brain signals. However, we should expect that there is no one-to-one mapping between the observed phase lag and the time precedence as specified by physically interacting systems. Specifically, phase lag observed between two signals may interfere with inferring causal relations. This could be of critical importance for the coupled non-linear oscillating systems, with possible time delays in coupling, when classical linear cross-spectrum strategies for solving phase ambiguity are not efficient. To demonstrate this, we used a prototypical model of coupled non-linear systems, and compared three typical pipelines of inferring Granger causality, as established in the literature. Specifically, we compared the performance of the spectral and information-theoretic Granger pipelines as well as standard Granger causality in their relations to the observed phase differences for frequencies at which the signals become synchronized to each other. We found that an information-theoretic approach, which takes into account different time lags between the past of one signal and the future of another signal, was the most robust to phase effects. PMID:23349720

  12. Event-related potential indices of congruency sequence effects without feature integration or contingency learning confounds.

    PubMed

    Larson, Michael J; Clayson, Peter E; Kirwan, C Brock; Weissman, Daniel H

    2016-06-01

    The congruency effect in Stroop-like tasks (i.e., increased response time and reduced accuracy in incongruent relative to congruent trials) is often smaller when the previous trial was incongruent as compared to congruent. This congruency sequence effect (CSE) is thought to reflect cognitive control processes that shift attention to the target and/or modulate the response engendered by the distracter differently after incongruent relative to congruent trials. The neural signatures of CSEs are therefore usually attributed to cognitive control processes that minimize distraction from irrelevant stimuli. However, CSEs in previous functional neuroimaging studies were ubiquitously confounded with feature integration and/or contingency learning processes. We therefore investigated whether a neural CSE can be observed without such confounds in a group of healthy young adults (n = 56). To this end, we combined a prime-probe task that lacks such confounds with high-density ERPs to identify, for the first time, the neural time course of confound-minimized CSEs. Replicating recent behavioral findings, we observed strong CSEs in this task for mean response time and mean accuracy. Critically, conceptually replicating prior ERP results from confounded tasks, we also observed a CSE in both the parietal conflict slow potential (conflict SP) and the frontomedial N450. These findings indicate for the first time that neural CSEs as indexed by ERPs can be observed without the typical confounds. More broadly, the present study provides a confound-minimized protocol that will help future researchers to better isolate the neural bases of control processes that minimize distraction from irrelevant stimuli. PMID:26854028

  13. EVALUATING COSTS WITH UNMEASURED CONFOUNDING: A SENSITIVITY ANALYSIS FOR THE TREATMENT EFFECT

    PubMed Central

    Handorf, Elizabeth A.; Bekelman, Justin E.; Heitjan, Daniel F.; Mitra, Nandita

    2014-01-01

    Estimates of the effects of treatment on cost from observational studies are subject to bias if there are unmeasured confounders. It is therefore advisable in practice to assess the potential magnitude of such biases. We derive a general adjustment formula for loglinear models of mean cost and explore special cases under plausible assumptions about the distribution of the unmeasured confounder. We assess the performance of the adjustment by simulation, in particular, examining robustness to a key assumption of conditional independence between the unmeasured and measured covariates given the treatment indicator. We apply our method to SEER-Medicare cost data for a stage II/III muscle-invasive bladder cancer cohort. We evaluate the costs for radical cystectomy vs. combined radiation/chemotherapy, and find that the significance of the treatment effect is sensitive to plausible unmeasured Bernoulli, Poisson and Gamma confounders. PMID:24587844

  14. Consistent causal effect estimation under dual misspecification and implications for confounder selection procedures

    PubMed Central

    Gruber, Susan; van der Laan, Mark J

    2014-01-01

    In a previously published article in this journal, Vansteeland et al. [Stat Methods Med Res. Epub ahead of print 12 November 2010. DOI: 10.1177/0962280210387717] address confounder selection in the context of causal effect estimation in observational studies. They discuss several selection strategies and propose a procedure whose performance is guided by the quality of the exposure effect estimator. The authors note that when a particular linearity condition is met, consistent estimation of the target parameter can be achieved even under dual misspecification of models for the association of confounders with exposure and outcome and demonstrate the performance of their procedure relative to other estimators when this condition holds. Our earlier published work on collaborative targeted minimum loss based learning provides a general theoretical framework for effective confounder selection that explains the findings of Vansteelandt et al. and underscores the appropriateness of their suggestions that a confounder selection procedure should be concerned with directly targeting the quality of the estimate and that desirable estimators produce valid confidence intervals and are robust to dual misspecification. PMID:22368176

  15. Health Effects of Lesion Localization in Multiple Sclerosis: Spatial Registration and Confounding Adjustment

    PubMed Central

    Eloyan, Ani; Shou, Haochang; Shinohara, Russell T.; Sweeney, Elizabeth M.; Nebel, Mary Beth; Cuzzocreo, Jennifer L.; Calabresi, Peter A.; Reich, Daniel S.; Lindquist, Martin A.; Crainiceanu, Ciprian M.

    2014-01-01

    Brain lesion localization in multiple sclerosis (MS) is thought to be associated with the type and severity of adverse health effects. However, several factors hinder statistical analyses of such associations using large MRI datasets: 1) spatial registration algorithms developed for healthy individuals may be less effective on diseased brains and lead to different spatial distributions of lesions; 2) interpretation of results requires the careful selection of confounders; and 3) most approaches have focused on voxel-wise regression approaches. In this paper, we evaluated the performance of five registration algorithms and observed that conclusions regarding lesion localization can vary substantially with the choice of registration algorithm. Methods for dealing with confounding factors due to differences in disease duration and local lesion volume are introduced. Voxel-wise regression is then extended by the introduction of a metric that measures the distance between a patient-specific lesion mask and the population prevalence map. PMID:25233361

  16. The confounding effect of cryptic relatedness for environmental risks of systolic blood pressure on cohort studies

    PubMed Central

    Shibata, Kyoko; Hozawa, Atsushi; Tamiya, Gen; Ueki, Masao; Nakamura, Tomohiro; Narimatsu, Hiroto; Kubota, Isao; Ueno, Yoshiyuki; Kato, Takeo; Yamashita, Hidetoshi; Fukao, Akira; Kayama, Takamasa

    2013-01-01

    The impact of cryptic relatedness (CR) on genomic association studies is well studied and known to inflate false-positive rates as reported by several groups. In contrast, conventional epidemiological studies for environmental risks, the confounding effect of CR is still uninvestigated. In this study, we investigated the confounding effect of unadjusted CR among a rural cohort in the relationship between environmental risk factors (body mass index, smoking status, alcohol consumption) and systolic blood pressure. We applied the methods of population-based whole-genome association studies for the analysis of the genome-wide single nucleotide polymorphism data in 1622 subjects, and detected 20.2% CR in this cohort population. In the case of the sample size, approximately 1000, the ratio of CR to the population was 20.2%, the population prevalence 25%, the prevalence in the CR 26%, heritability for liability 14.3% and prevalence in the subpopulation without CR 26%, the difference of estimated regression coefficient between samples with and without CR was not significant (P-value = 0.55). On the other hand, in another case with approximately >20% heritability for liability, we showed that confounding due to CR biased the estimation of exposure effects. PMID:24498600

  17. The confounding effect of cryptic relatedness for environmental risks of systolic blood pressure on cohort studies.

    PubMed

    Shibata, Kyoko; Hozawa, Atsushi; Tamiya, Gen; Ueki, Masao; Nakamura, Tomohiro; Narimatsu, Hiroto; Kubota, Isao; Ueno, Yoshiyuki; Kato, Takeo; Yamashita, Hidetoshi; Fukao, Akira; Kayama, Takamasa

    2013-05-01

    The impact of cryptic relatedness (CR) on genomic association studies is well studied and known to inflate false-positive rates as reported by several groups. In contrast, conventional epidemiological studies for environmental risks, the confounding effect of CR is still uninvestigated. In this study, we investigated the confounding effect of unadjusted CR among a rural cohort in the relationship between environmental risk factors (body mass index, smoking status, alcohol consumption) and systolic blood pressure. We applied the methods of population-based whole-genome association studies for the analysis of the genome-wide single nucleotide polymorphism data in 1622 subjects, and detected 20.2% CR in this cohort population. In the case of the sample size, approximately 1000, the ratio of CR to the population was 20.2%, the population prevalence 25%, the prevalence in the CR 26%, heritability for liability 14.3% and prevalence in the subpopulation without CR 26%, the difference of estimated regression coefficient between samples with and without CR was not significant (P-value = 0.55). On the other hand, in another case with approximately >20% heritability for liability, we showed that confounding due to CR biased the estimation of exposure effects. PMID:24498600

  18. Sensitivity analysis for direct and indirect effects in the presence of exposure-induced mediator-outcome confounders

    PubMed Central

    Chiba, Yasutaka

    2014-01-01

    Questions of mediation are often of interest in reasoning about mechanisms, and methods have been developed to address these questions. However, these methods make strong assumptions about the absence of confounding. Even if exposure is randomized, there may be mediator-outcome confounding variables. Inference about direct and indirect effects is particularly challenging if these mediator-outcome confounders are affected by the exposure because in this case these effects are not identified irrespective of whether data is available on these exposure-induced mediator-outcome confounders. In this paper, we provide a sensitivity analysis technique for natural direct and indirect effects that is applicable even if there are mediator-outcome confounders affected by the exposure. We give techniques for both the difference and risk ratio scales and compare the technique to other possible approaches. PMID:25580387

  19. Accounting for Uncertainty in Confounder and Effect Modifier Selection when Estimating Average Causal Effects in Generalized Linear Models

    PubMed Central

    Wang, Chi; Dominici, Francesca; Parmigiani, Giovanni; Zigler, Corwin Matthew

    2015-01-01

    Summary Confounder selection and adjustment are essential elements of assessing the causal effect of an exposure or treatment in observational studies. Building upon work by Wang et al. (2012) and Lefebvre et al. (2014), we propose and evaluate a Bayesian method to estimate average causal effects in studies with a large number of potential confounders, relatively few observations, likely interactions between confounders and the exposure of interest, and uncertainty on which confounders and interaction terms should be included. Our method is applicable across all exposures and outcomes that can be handled through generalized linear models. In this general setting, estimation of the average causal effect is different from estimation of the exposure coefficient in the outcome model due to non-collapsibility. We implement a Bayesian bootstrap procedure to integrate over the distribution of potential confounders and to estimate the causal effect. Our method permits estimation of both the overall population causal effect and effects in specified subpopulations, providing clear characterization of heterogeneous exposure effects that may vary considerably across different covariate profiles. Simulation studies demonstrate that the proposed method performs well in small sample size situations with 100 to 150 observations and 50 covariates. The method is applied to data on 15060 US Medicare beneficiaries diagnosed with a malignant brain tumor between 2000 and 2009 to evaluate whether surgery reduces hospital readmissions within thirty days of diagnosis. PMID:25899155

  20. The Effect of Clozapine on Premature Mortality: An Assessment of Clinical Monitoring and Other Potential Confounders

    PubMed Central

    Hayes, Richard D.; Downs, Johnny; Chang, Chin-Kuo; Jackson, Richard G.; Shetty, Hitesh; Broadbent, Matthew; Hotopf, Matthew; Stewart, Robert

    2015-01-01

    Clozapine can cause severe adverse effects yet it is associated with reduced mortality risk. We test the hypothesis this association is due to increased clinical monitoring and investigate risk of premature mortality from natural causes. We identified 14 754 individuals (879 deaths) with serious mental illness (SMI) including schizophrenia, schizoaffective and bipolar disorders aged ≥ 15 years in a large specialist mental healthcare case register linked to national mortality tracing. In this cohort study we modeled the effect of clozapine on mortality over a 5-year period (2007–2011) using Cox regression. Individuals prescribed clozapine had more severe psychopathology and poorer functional status. Many of the exposures associated with clozapine use were themselves risk factors for increased mortality. However, we identified a strong association between being prescribed clozapine and lower mortality which persisted after controlling for a broad range of potential confounders including clinical monitoring and markers of disease severity (adjusted hazard ratio 0.4; 95% CI 0.2–0.7; p = .001). This association remained after restricting the sample to those with a diagnosis of schizophrenia or those taking antipsychotics and after using propensity scores to reduce the impact of confounding by indication. Among individuals with SMI, those prescribed clozapine had a reduced risk of mortality due to both natural and unnatural causes. We found no evidence to indicate that lower mortality associated with clozapine in SMI was due to increased clinical monitoring or confounding factors. This is the first study to report an association between clozapine and reduced risk of mortality from natural causes. PMID:25154620

  1. Task-independent effects are potential confounders in longitudinal imaging studies of learning in schizophrenia

    PubMed Central

    Korostil, Michele; Fatima, Zainab; Kovacevic, Natasha; Menon, Mahesh; McIntosh, Anthony Randal

    2015-01-01

    Learning impairment is a core deficit in schizophrenia that impacts on real-world functioning and yet, elucidating its underlying neural basis remains a challenge. A key issue when interpreting learning-task experiments is that task-independent changes may confound interpretation of task-related signal changes in neuroimaging studies. The nature of these task-independent changes in schizophrenia is unknown. Therefore, we examined task-independent “time effects” in a group of participants with schizophrenia contrasted with healthy participants in a longitudinal fMRI learning-experiment designed to allow for examination of non-specific effects of time. Flanking the learning portions of the experiment with a task-of-no-interest allowed us to extract task-independent BOLD changes. Task-independent effects occurred in both groups, but were more robust in the schizophrenia group. There was a significant interaction effect between group and time in a distributed activity pattern that included inferior and superior temporal regions, frontal areas (left anterior insula and superior medial gyri), and parietal areas (posterior cingulate cortices and precuneus). This pattern showed task-independent linear decrease in BOLD amplitude over the two scanning sessions for the schizophrenia group, but showed either opposite effect or no activity changes for the control group. There was a trend towards a correlation between task-independent effects and the presence of more negative symptoms in the schizophrenia group. The strong interaction between group and time suggests that both the scanning experience as a whole and the transition between task-types evokes a different response in persons with schizophrenia and may confound interpretation of learning-related longitudinal imaging experiments if not explicitly considered. PMID:26759790

  2. Confounding factors in HGT detection: statistical error, coalescent effects, and multiple solutions.

    PubMed

    Than, Cuong; Ruths, Derek; Innan, Hideki; Nakhleh, Luay

    2007-05-01

    Prokaryotic organisms share genetic material across species boundaries by means of a process known as horizontal gene transfer (HGT). This process has great significance for understanding prokaryotic genome diversification and unraveling their complexities. Phylogeny-based detection of HGT is one of the most commonly used methods for this task, and is based on the fundamental fact that HGT may cause gene trees to disagree with one another, as well as with the species phylogeny. Using these methods, we can compare gene and species trees, and infer a set of HGT events to reconcile the differences among these trees. In this paper, we address three factors that confound the detection of the true HGT events, including the donors and recipients of horizontally transferred genes. First, we study experimentally the effects of error in the estimated gene trees (statistical error) on the accuracy of inferred HGT events. Our results indicate that statistical error leads to overestimation of the number of HGT events, and that HGT detection methods should be designed with unresolved gene trees in mind. Second, we demonstrate, both theoretically and empirically, that based on topological comparison alone, the number of HGT scenarios that reconcile a pair of species/gene trees may be exponential. This number may be reduced when branch lengths in both trees are estimated correctly. This set of results implies that in the absence of additional biological information, and/or a biological model of how HGT occurs, multiple HGT scenarios must be sought, and efficient strategies for how to enumerate such solutions must be developed. Third, we address the issue of lineage sorting, how it confounds HGT detection, and how to incorporate it with HGT into a single stochastic framework that distinguishes between the two events by extending population genetics theories. This result is very important, particularly when analyzing closely related organisms, where coalescent effects may not be

  3. Reproductive and socioeconomic determinants of child survival: confounded, interactive, and age-dependent effects.

    PubMed

    Kost, K; Amin, S

    1992-01-01

    Studies of infant and child mortality have evolved to distinguish between two sets of explanatory variables-factors related to reproductive or maternal characteristics and socioeconomic factors, generally described as characteristics of the family or household. Almost all multivariate analyses include variables from each of these two sets, but there has been little consideration of the relationship between them. We examine how these two sets of variables jointly affect mortality. We test first for confounded effects by examining socioeconomic effects while excluding and then including reproductive variables in nested multivariate models. Next, we look for age-dependent effects among the explanatory variables and find that reproductive and socioeconomic factors affect mortality at differing ages of children. Finally, we examine interactive effects of the two sets of variables. We conclude that the higher mortality observed among the low status groups is not a result of greater concentration of poor reproductive patterns in those groups. Instead, higher status groups probably have more resources available for combating the negative effects of the same high-risk reproductive patterns. PMID:1514117

  4. A causal examination of the effects of confounding factors on multimetric indices

    USGS Publications Warehouse

    Schoolmaster, Donald R., Jr.; Grace, James B.; Schweiger, E. William; Mitchell, Brian R.; Guntenspergen, Glenn R.

    2013-01-01

    The development of multimetric indices (MMIs) as a means of providing integrative measures of ecosystem condition is becoming widespread. An increasingly recognized problem for the interpretability of MMIs is controlling for the potentially confounding influences of environmental covariates. Most common approaches to handling covariates are based on simple notions of statistical control, leaving the causal implications of covariates and their adjustment unstated. In this paper, we use graphical models to examine some of the potential impacts of environmental covariates on the observed signals between human disturbance and potential response metrics. Using simulations based on various causal networks, we show how environmental covariates can both obscure and exaggerate the effects of human disturbance on individual metrics. We then examine from a causal interpretation standpoint the common practice of adjusting ecological metrics for environmental influences using only the set of sites deemed to be in reference condition. We present and examine the performance of an alternative approach to metric adjustment that uses the whole set of sites and models both environmental and human disturbance effects simultaneously. The findings from our analyses indicate that failing to model and adjust metrics can result in a systematic bias towards those metrics in which environmental covariates function to artificially strengthen the metric–disturbance relationship resulting in MMIs that do not accurately measure impacts of human disturbance. We also find that a “whole-set modeling approach” requires fewer assumptions and is more efficient with the given information than the more commonly applied “reference-set” approach.

  5. Diffusion Tensor Imaging in Young Children with Autism: Biological Effects and Potential Confounds

    PubMed Central

    Walker, Lindsay; Gozzi, Marta; Lenroot, Rhoshel; Thurm, Audrey; Behseta, Babak; Swedo, Susan; Pierpaoli, Carlo

    2012-01-01

    Background Diffusion tensor imaging (DTI) has been used over the past decade to study structural differences in the brains of children with autism compared to typically developing children. These studies generally find reduced fractional anisotropy (FA) and increased mean diffusivity (MD) in children with autism, however the regional pattern of findings varies greatly. Methods We used DTI to investigate the brains of sedated children with autism (N=39) and naturally asleep typically developing children (N=39) between 2 and 8 years of age. Tract Based Spatial Statistics (TBSS) and whole brain voxel-wise analysis were performed to investigate the regional distribution of differences between groups. Results In children with autism, we found significantly reduced FA in widespread regions, and increased MD only in posterior brain regions. Significant age by group interaction was found, indicating a difference in developmental trends of FA and MD between children with autism and typically developing children. The magnitude of the measured differences between groups was small, on the order of ~1–2%. Subjects and controls showed distinct regional differences in imaging artifacts that can affect DTI measures. Conclusions We found statistically significant differences in DTI metrics between children with autism and typically developing children, including different developmental trends of these metrics. However, this study indicates that between-group differences in DTI studies of autism should be interpreted with caution, as their small magnitude make these measurements particularly vulnerable to the effects of artifacts and confounds, which may lead to false positive and/or false negative biological inferences. PMID:22906515

  6. Understanding Confounding Effects in Linguistic Coordination: An Information-Theoretic Approach

    PubMed Central

    Gao, Shuyang; Ver Steeg, Greg; Galstyan, Aram

    2015-01-01

    We suggest an information-theoretic approach for measuring stylistic coordination in dialogues. The proposed measure has a simple predictive interpretation and can account for various confounding factors through proper conditioning. We revisit some of the previous studies that reported strong signatures of stylistic accommodation, and find that a significant part of the observed coordination can be attributed to a simple confounding effect—length coordination. Specifically, longer utterances tend to be followed by longer responses, which gives rise to spurious correlations in the other stylistic features. We propose a test to distinguish correlations in length due to contextual factors (topic of conversation, user verbosity, etc.) and turn-by-turn coordination. We also suggest a test to identify whether stylistic coordination persists even after accounting for length coordination and contextual factors. PMID:26115446

  7. Wind turbines and idiopathic symptoms: The confounding effect of concurrent environmental exposures.

    PubMed

    Blanes-Vidal, Victoria; Schwartz, Joel

    2016-01-01

    Whether or not wind turbines pose a risk to human health is a matter of heated debate. Personal reactions to other environmental exposures occurring in the same settings as wind turbines may be responsible of the reported symptoms. However, these have not been accounted for in previous studies. We investigated whether there is an association between residential proximity to wind turbines and idiopathic symptoms, after controlling for personal reactions to other environmental co-exposures. We assessed wind turbine exposures in 454 residences as the distance to the closest wind turbine (Dw) and number of wind turbines <1000m (Nw1000). Information on symptoms, demographics and personal reactions to exposures was obtained by a blind questionnaire. We identified confounders using confounders' selection criteria and used adjusted logistic regression models to estimate associations. When controlling only for socio-demographic characteristics, log10Dw was associated with "unnatural fatigue" (ORadj=0.38, 95%CI=0.15-1.00) and "difficulty concentrating" (ORadj=0.26, 95%CI=0.08-0.83) and Nw1000 was associated with "unnatural fatigue" (ORadj=1.35, 95%CI=1.07-1.70) and "headache" (ORadj=1.26, 95%CI=1.00-1.58). After controlling for personal reactions to noise from sources different from wind turbines and agricultural odor exposure, we did not observe a significant relationship between residential proximity to wind turbines and symptoms and the parameter estimates were attenuated toward zero. Wind turbines-health associations can be confounded by personal reactions to other environmental co-exposures. Isolated associations reported in the literature may be due to confounding bias. PMID:27046778

  8. Are the apparent effects of cigarette smoking on lung and bladder cancers due to uncontrolled confounding by occupational exposures?

    PubMed

    Siemiatycki, J; Dewar, R; Krewski, D; Désy, M; Richardson, L; Franco, E

    1994-01-01

    It has been suggested that the well known associations between smoking and cancer may in part reflect inadequately controlled confounding due to occupational exposures. The purpose of the present analysis is to describe the association between cigarette smoking and both lung and bladder cancers, taking into account the potential confounding effects of over 300 covariates, most of which represent occupational exposures. A population-based case-control study was undertaken in Montreal to investigate the associations between a large variety of environmental and occupational exposures, on the one hand, and several types of cancer, on the other. Interviews were carried out with male incident cases of several sites of cancer, including 857 lung cancers and 484 bladder cancers. A group of non-smoking-related cancers, comprising 1,707 interviewed subjects, was used as one control group. Additionally, 533 population controls were interviewed and constituted a second control group. Interview information included detailed lifetime smoking histories, job histories, and other potential confounders. Each job history was reviewed by a team of experts who translated it into a history of occupational exposures. These occupational exposures, as well as nonoccupational covariates, were treated as potential confounders in the analysis of cigarette smoking effects. Regardless of whether population controls or cancer controls were used, the odds ratio (OR) between smoking and lung cancer (ranging from 12 to 16 for ever vs never smokers) was not materially affected by adjustment for occupational exposures. The odds ratios for bladder cancer (ranging from 2 to 3) were also unaffected by confounding due to occupational exposures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8117783

  9. Examining the Relationship between Heavy Alcohol Use and Assaults: With Adjustment for the Effects of Unmeasured Confounders

    PubMed Central

    Liang, Wenbin; Chikritzhs, Tanya

    2015-01-01

    Background. Experimental studies suggest that alcohol can lead to aggression in laboratory settings; however, it is impossible to test the causal relationship between alcohol use and real-life violence among humans in randomized clinical trials. Objectives. (i) To examine the relationship between heavy alcohol use and assaults in a population based study; (ii) to demonstrate the proxy outcome method, as a means of controlling the effects of unknown/unmeasured confounders in observational studies. Methods. This study used data collected from three waves of the National Survey on Drug Use and Health (NSDUH). The effects of heavy alcohol use on assault were measured using multivariable logistic regressions in conjunction with the proxy outcome method. Results. Application of the proxy outcome method indicated that effect sizes of heavy alcohol use on the risk of assault were overestimated in the standard models. After adjusting for the effects of unknown/unmeasured confounders, the risk of assault remained 43% and 63% higher (P < 0.05) among participants who consumed 5+ drinks/day for 5–8 days/month and 9–30 days/month, respectively. Conclusions. Even after adjustment for unknown/unmeasured confounders the association between heavy alcohol use and risk of violence remained significant. These findings support the hypothesis that heavy alcohol use can cause violence. PMID:26380283

  10. Potential confounding effects of benzyl alcohol as a formulation excipient support the elimination of the abnormal toxicity test from pharmacopoeias.

    PubMed

    Xie, Jianxun; Ottaviani, Giorgio; Sun, Kai; Lu, Mingqiu; Wu, Xiaoqin; Huang, Sunfeng; Bopst, Martin

    2015-11-01

    Benzyl alcohol is an excipient used in many drugs as a stabilizer. Depending on the amount present in drug formulations there might be confounding findings in the Abnormal Toxicity Test (ATT). The ATT is utilized as a quality control (QC) release test to detect extraneous contaminants according to national pharmacopoeias. Our study assessed the effects of benzyl alcohol as defined in ATT designs. This study - the first thorough evaluation of the confounding effects of benzyl alcohol on the ATT - was conducted in relation to particular health authority questions and was part of the root-cause analyses resulting from some transient behavioral findings observed in the test. Two strains of mice, CD-1 & Kunming, plus Hartley guinea pigs were administered intraperitoneally (ip), subcutaneously (sc), or intravenously (iv) with benzyl alcohol at dose level defined in the ATT design. In both mice and guinea pigs, only after ip administration, minimal behavioral changes were observed transiently within 2-3 min after administration. Therefore, the presence of benzyl alcohol in the product batch may confound the ATT results. This study provides further evidence to question the validity of the ATT for its intended use. PMID:26449397

  11. Depression and Physical Inactivity as Confounding the Effect of Obesity on Atrial Fibrillation.

    PubMed

    Garimella, Roja S; Sears, Samuel F; Gehi, Anil K

    2016-06-01

    Obesity is associated with an increased likelihood for the development of atrial fibrillation (AF) and with worsened AF symptom severity. However, other factors that are correlated with obesity may confound or mediate the relation of obesity with AF symptom severity. The purpose of this study was to determine if depression and physical inactivity may confound the association of obesity and AF symptom severity. Health status and demographic data were captured by questionnaire for 332 outpatients with documented AF. Weight/height was measured and body mass index (kg/m(2)) calculated. Recent depression symptom severity was assessed using the Patient Health Questionnaire-9 questionnaire. Physical activity during the last month was assessed by questionnaire. AF symptom severity was assessed using the University of Toronto AF Severity scale. Multivariate linear regression was used to evaluate which factors were associated with AF symptom severity. Obesity in patients with AF is associated with increased depression severity. In bivariate analysis, increasing body mass index (p = 0.001), lower levels of physical activity (p <0.001), and more severe depression (p <0.001) were associated with worsened AF symptom severity. In multivariate analysis, only physical activity and depression persisted as significant predictors of AF symptom severity. In conclusion, although obesity likely contributes to the substrate predisposing to the development of AF, other factors may contribute to or mediate the worsened AF symptoms associated with obesity. Depression symptoms and physical inactivity, factors closely correlated with obesity, may exacerbate symptoms in patients with AF. PMID:27067618

  12. Measuring oxidative stress: the confounding effect of lipid concentration in measures of lipid peroxidation.

    PubMed

    Pérez-Rodríguez, Lorenzo; Romero-Haro, Ana A; Sternalski, Audrey; Muriel, Jaime; Mougeot, Francois; Gil, Diego; Alonso-Alvarez, Carlos

    2015-01-01

    Lipid peroxidation products are widely used as markers of oxidative damage in the organism. To properly interpret the information provided by these markers, it is necessary to know potential sources of bias and control confounding factors. Here, we investigated the relationship between two indicators of lipid mobilization (circulating levels of triglycerides and cholesterol) and two common markers of oxidative damage (plasma levels of malondialdehyde and hydroperoxides; the latter estimated from the d-ROMs assay kit). The following five avian species were studied: red-legged partridge (Alectoris rufa), zebra finch (Taeniopygia guttata), spotless starling (Sturnus unicolor), marsh harrier (Circus aeroginosus), and Montagu's harrier (Circus pygargus). In all cases, plasma triglyceride levels positively and significantly correlated with lipid peroxidation markers, explaining between 8% and 34% of their variability. Plasma cholesterol, in contrast, showed a significant positive relationship only among spotless starling nestlings and a marginally significant association in zebra finches. These results indicate that lipid peroxidation marker levels covary with circulating lipid levels. We discuss the potential causes and implications of this covariation and recommend that future studies that measure oxidative damage using lipid peroxidation markers report both raw and relative levels (i.e., corrected for circulating triglycerides). Whether the observed pattern also holds for other tissues and in other taxa would deserve further research. PMID:25860832

  13. A principal stratification approach for evaluating natural direct and indirect effects in the presence of treatment-induced intermediate confounding.

    PubMed

    Taguri, Masataka; Chiba, Yasutaka

    2015-01-15

    Recently, several authors have shown that natural direct and indirect effects (NDEs and NIEs) can be identified under the sequential ignorability assumptions, as long as there is no mediator-outcome confounder that is affected by the treatment. However, if such a confounder exists, NDEs and NIEs will generally not be identified without making additional identifying assumptions. In this article, we propose novel identification assumptions and estimators for evaluating NDEs and NIEs under the usual sequential ignorability assumptions, using the principal stratification framework. It is assumed that the treatment and the mediator are dichotomous. We must impose strong assumptions for identification. However, even if these assumptions were violated, the bias of our estimator would be small under typical conditions, which can be easily evaluated from the observed data. This conjecture is confirmed for binary outcomes by deriving the bounds of the bias terms. In addition, the advantage of our estimator is illustrated through a simulation study. We also propose a method of sensitivity analysis that examines what happens when our assumptions are violated. We apply the proposed method to data from the National Center for Health Statistics. PMID:25312003

  14. Disentangling the confounding effects of PAR and air temperature on net ecosystem exchange in time and scale

    NASA Astrophysics Data System (ADS)

    yang, Z.; Chen, J.; Becker, R.; Chu, H.; Xie, J.; Shao, C.

    2013-12-01

    Net ecosystem exchange of CO2 (NEE) in temperate forests is modulated by microclimatic factors. The effects of those factors differ at different time scales and during different time periods. Some of them are correlated across a number of time scales, so their effects on NEE are confounded by each other. PAR and air temperature (Ta) are among the two most important drivers of NEE in temperate forests, and among the two most correlated microclimatic factors. PAR and Ta have similar daily, seasonal, and annual cycles. Their influence on NEE is confounded by each other and entangled together especially at those scales. In this study, we tried to disentangle the confounding effects of them on NEE at different time scales and during different time periods. To accomplish this objective, we applied the innovative spectral analysis techniques including Continuous Wavelet Transformation (CWT), Cross Wavelet Transformation (XWT), Wavelet Coherent (WTC), and Partial Wavelet Coherence (PWC) on seven years time series (2004-2010) of PAR, Ta and NEE from the Ohio Oak Openings site (N 41.5545°, W 83.8438°), USA for spectral analysis. We found that PAR is the major driver at short time scales (e.g. semidiurnal and daily) and Ta is the major driver at long time scales (e.g. seasonal and annual). At daily scale during growing seasons, PAR is anti-phase with NEE with no time delay while Ta lagged PAR about 2-3 hours, which could be explained by the strong dependence of photosynthesis on PAR and a 2-3 hours lags of the daily course of Ta to PAR. At daily scale during non-growing season, NEE has little variation and thus neither Ta nor PAR has high common wavelet power and significant coherence with NEE. At annual scale, Ta is anti-phase with NEE and PAR leads NEE about 34 days, which could be explained by the strong dependence of LAI dynamics on Ta and the lag between the LAI/biomass development and the progress of sunlight. We also found that NEE distributes most of its variation

  15. When can we measure stress noninvasively? Postdeposition effects on a fecal stress metric confound a multiregional assessment.

    PubMed

    Wilkening, Jennifer L; Ray, Chris; Varner, Johanna

    2016-01-01

    Measurement of stress hormone metabolites in fecal samples has become a common method to assess physiological stress in wildlife populations. Glucocorticoid metabolite (GCM) measurements can be collected noninvasively, and studies relating this stress metric to anthropogenic disturbance are increasing. However, environmental characteristics (e.g., temperature) can alter measured GCM concentration when fecal samples cannot be collected immediately after defecation. This effect can confound efforts to separate environmental factors causing predeposition physiological stress in an individual from those acting on a fecal sample postdeposition. We used fecal samples from American pikas (Ochotona princeps) to examine the influence of environmental conditions on GCM concentration by (1) comparing GCM concentration measured in freshly collected control samples to those placed in natural habitats for timed exposure, and (2) relating GCM concentration in samples collected noninvasively throughout the western United States to local environmental characteristics measured before and after deposition. Our timed-exposure trials clarified the spatial scale at which exposure to environmental factors postdeposition influences GCM concentration in pika feces. Also, fecal samples collected from occupied pika habitats throughout the species' range revealed significant relationships between GCM and metrics of climate during the postdeposition period (maximum temperature, minimum temperature, and precipitation during the month of sample collection). Conversely, we found no such relationships between GCM and metrics of climate during the predeposition period (prior to the month of sample collection). Together, these results indicate that noninvasive measurement of physiological stress in pikas across the western US may be confounded by climatic conditions in the postdeposition environment when samples cannot be collected immediately after defecation. Our results reiterate the importance

  16. Confounding effects of aqueous-phase impinger chemistry on apparent oxidation of mercury in flue gases

    SciTech Connect

    Brydger Cauch; Geoffrey D. Silcox; Joann S. Lighty; Jost O.L. Wendt; Andrew Fry; Constance L. Senior

    2008-04-01

    Gas-phase reactions between elemental mercury and chlorine are a possible pathway to producing oxidized mercury species such as mercuric chloride in combustion systems. This study examines the effect of the chemistry of a commonly used sample conditioning system on apparent and actual levels of mercury oxidation in a methane-fired, 0.3 kW, quartz-lined reactor in which gas composition (HCl, Cl{sub 2}, NOx, SO{sub 2}) and quench rate were varied. The sample conditioning system included two impingers in parallel: one containing an aqueous solution of KCl to trap HgCl{sub 2}, and one containing an aqueous solution of SnCl{sub 2} to reduce HgCl{sub 2} to elemental mercury (Hg{sup 0}). Gas-phase concentrations of Cl{sub 2} as low as 1.5 ppmv were sufficient to oxidize a significant fraction of the elemental mercury in the KCl impinger via the hypochlorite ion. Furthermore, these low, but interfering levels of Cl{sub 2} appeared to persist in flue gases from several doped rapidly mixed flames with varied post flame temperature quench rates. The addition of 0.5 wt% sodium thiosulfate to the KCl solution completely prevented the oxidation from occurring in the impinger. The addition of thiosulfate did not inhibit the KCl impinger's ability to capture HgCl{sub 2}. The effectiveness of the thiosulfate was unchanged by NO or SO{sub 2}. These results bring into question laboratory scale experimental data on mercury oxidation where wet chemistry was used to partition metallic and oxidized mercury without the presence of sufficient levels of SO{sub 2}. 23 refs., 5 figs., 1 tab.

  17. Severity grading of chronic obstructive pulmonary disease: the confounding effect of phenotype and thoracic gas compression.

    PubMed

    Pellegrino, Riccardo; Crimi, Emanuele; Gobbi, Alessandro; Torchio, Roberto; Antonelli, Andrea; Gulotta, Carlo; Baroffio, Michele; Papa, Giuseppe Francesco Sferrazza; Dellacà, Raffaele; Brusasco, Vito

    2015-04-01

    Current guidelines recommend severity of chronic obstructive pulmonary disease be graded by using forced expiratory volume in 1 s (FEV1). But this measurement is biased by thoracic gas compression depending on lung volume and airflow resistance. The aim of this study was to test the hypothesis that the effect of thoracic gas compression on FEV1 is greater in emphysema than chronic bronchitis because of larger lung volumes, and this influences severity classification and prognosis. FEV1 was simultaneously measured by spirometry and body plethysmography (FEV1-pl) in 47 subjects with dominant emphysema and 51 with dominant chronic bronchitis. Subjects with dominant emphysema had larger lung volumes, lower diffusion capacity, and lower FEV1 than those with dominant chronic bronchitis. However, FEV1-pl, patient-centered variables (dyspnea, quality of life, exercise tolerance, exacerbation frequency), arterial blood gases, and respiratory impedance were not significantly different between groups. Using FEV1-pl instead of FEV1 shifted severity distribution toward less severe classes in dominant emphysema more than chronic bronchitis. The body mass, obstruction, dyspnea, and exercise (BODE) index was significantly higher in dominant emphysema than chronic bronchitis, but this difference significantly decreased when FEV1-pl was substituted for FEV1. In conclusion, the FEV1 is biased by thoracic gas compression more in subjects with dominant emphysema than in those with chronic bronchitis. This variably and significantly affects the severity grading systems currently recommended. PMID:25414244

  18. Selective predation on hantavirus-infected voles by owls and confounding effects from landscape properties.

    PubMed

    Khalil, Hussein; Ecke, Frauke; Evander, Magnus; Hörnfeldt, Birger

    2016-06-01

    It has been suggested that predators may protect human health through reducing disease-host densities or selectively preying on infected individuals from the population. However, this has not been tested empirically. We hypothesized that Tengmalm's owl (Aegolius funereus) selectively preys on hantavirus-infected individuals of its staple prey, the bank vole (Myodes glareolus). Bank voles are hosts of Puumala hantavirus, which causes a form of hemorrhagic fever in humans. Selective predation by owls on infected voles may reduce human disease risk. We compared the prevalence of anti-Puumala hantavirus antibodies (seroprevalence), in bank voles cached by owls in nest boxes to seroprevalence in voles trapped in closed-canopy forest around each nest box. We found no general difference in seroprevalence. Forest landscape structure could partly account for the observed patterns in seroprevalence. Only in more connected forest patches was seroprevalence in bank voles cached in nest boxes higher than seroprevalence in trapped voles. This effect disappeared with increasing forest patch isolation, as seroprevalence in trapped voles increased with forest patch isolation, but did not in cached voles. Our results suggest a complex relationship between zoonotic disease prevalence in hosts, their predators, and landscape structure. Some mechanisms that may have caused the seroprevalence patterns in our results include higher bank vole density in isolated forest patches. This study offers future research potential to shed further light on the contribution of predators and landscape properties to human health. PMID:26873607

  19. The confounding effects of light, sonication, and Mn(III)TBAP on quantitation of superoxide using hydroethidine.

    PubMed

    Zielonka, Jacek; Vasquez-Vivar, Jeannette; Kalyanaraman, B

    2006-10-01

    Previously, we showed that hydroethidine (HE) reacts with intracellular superoxide radical anion (O2-*) to form a unique fluorescent marker product, 2-hydroxyethidium cation (2-OH-E+), that was not formed from HE reaction with other biologically relevant oxidants (H. Zhao et al. Proc. Natl. Acad. Sci. USA102:5727-5732; 2005). Here we rigorously assessed the confounding effects of light, sonication, and Mn(III)TBAP on 2-OH-E+, the HE/O2-* reaction product. Results indicate that continuous exposure to visible light induced photo-oxidation of HE to ethidium cation (E+) by a 2-OH-E+ -dependent mechanism. Treatment of HE with ultrasound, a frequently used technique to lyse cell membranes, induced 2-OH-E+ from in situ generation of O2-*. Mn(III)TBAP, a cell-permeable metal-porphyrin complex used as a catalytic antioxidant, reacts with HE to form E+. This finding provides an alternative interpretation for Mn(III)TBAP effects during the HE/O2-* reaction. In order to correctly interpret the HE reaction with O2-* in cells, it is therefore imperative that HE and HE-derived products be measured by HPLC. A new and improved HPLC-electrochemical (HPLC-EC) detection has been developed for analysis of intracellular O2-*. The HPLC-EC method is at least 10 times more sensitive than the HPLC-fluorescence technique for detecting O2-* in cells. PMID:16962930

  20. Are apparent negative effects of feeding GM MON810 maize to Atlantic salmon, Salmo salar, caused by confounding factors?

    PubMed

    Sissener, Nini H; Hemre, Gro-Ingunn; Lall, Santosh P; Sagstad, Anita; Petersen, Kjell; Williams, Jason; Rohloff, Jens; Sanden, Monica

    2011-07-01

    The present study was conducted to follow up on apparent differences in growth, relative organ sizes, cellular stress and immune function in Atlantic salmon fed feed containing GM Bacillus thuringiensis maize compared with feed containing the non-modified parental maize line. Gene expression profiling on the distal intestinal segment and liver was performed by microarray, and selected genes were followed up by quantitative PCR (qPCR). In the liver, qPCR revealed some differentially regulated genes, including up-regulation of gelsolin precursor, down-regulation of ferritin heavy subunit and a tendency towards down-regulation of metallothionein (MT)-B. This, combined with the up-regulation of anti-apoptotic protein NR13 and similar tendencies for ferritin heavy chain and MT-A and -B in the distal intestine, suggests changes in cellular stress/antioxidant status. This corresponds well with and strengthens previous findings in these fish. To exclude possible confounding factors, the maize ingredients were analysed for mycotoxins and metabolites. The GM maize contained 90 μg/kg of deoxynivalenol (DON), while the non-GM maize was below the detection limit. Differences were also observed in the metabolite profiles of the two maize varieties, some of which seemed connected to the mycotoxin level. The effects on salmon observed in the present and previous studies correspond relatively well with the effects of DON as reported in the literature for other production animals, but knowledge regarding effects and harmful dose levels in fish is scarce. Thus, it is difficult to conclude whether the observed effects are caused by the DON level or by some other aspect of the GM maize ingredient. PMID:21418706

  1. Confounding effect of EEG implantation surgery: Inadequacy of surgical control in a two hit model of temporal lobe epilepsy.

    PubMed

    Balzekas, Irena; Hernandez, Jose; White, Jacob; Koh, Sookyong

    2016-05-27

    In rodent models of epilepsy, EEG implantation surgery is an essential modality to evaluate electrographic seizures. The inflammatory consequences of EEG electrode-implantation and their resultant effects on seizure susceptibility are unclear. We evaluated electrode-implantation in a two-hit model of epileptogenesis in C57BL/6 mice that included brief, recurrent febrile seizures (FS) at P14 and kainic acid induced seizures (KA-SZ) at P28. During KA-SZ, latencies to first electrographic and behavioral seizures, seizure severity, and KA dose sensitivity were measured. Mice that received subdural screw electrode implants at P25 for EEG monitoring at P28 had significantly shorter latencies to seizures than sham mice, regardless of early life seizure experience. Electrode-implanted mice were sensitive to low dose KA as shown by high mortality rate at KA doses above 10mg/kg. We then directly compared electrode-implantation and KA-SZ in seizure naive CX3CR1(GFP/+) transgenic C57BL/6 mice, wherein microglia express green fluorescent protein (GFP), to determine if microglia activation related to surgery was associated with the increased seizure susceptibility in electrode-implanted mice from the two-hit model. Hippocampal microglia activation, as demonstrated by percent area GFP signal and GFP positive cell counts, prior to seizures was indistinguishable between electrode-implanted mice and controls, but was significantly greater in electrode-implanted mice following seizures. Electrode-implantation had a confounding priming effect on the inflammatory response to subsequent seizures. PMID:27095588

  2. The essence of linkage-based imprinting detection: comparing power, type 1 error, and the effects of confounders in two different analysis approaches.

    PubMed

    Greenberg, David A; Monti, Maria Cristina; Feenstra, Bjarke; Zhang, Junying; Hodge, Susan E

    2010-05-01

    Imprinting is critical to understanding disease expression. It can be detected using linkage information, but the effects of potential confounders (heterogeneity, sex-specific penetrance, and sex-biased ascertainment) have not been explored. We examine power and confounders in two imprinting detection approaches, and we explore imprinting-linkage interaction. One method (PP) models imprinting by maximising lod scores w.r.t. parent-specific penetrances. The second (DRF) approximates imprinting by maximising lods over differential male-female recombination fractions. We compared power, type 1 error, and confounder effects in these two methods, using computer-simulated data. We varied heterogeneity, penetrance, family and dataset size, and confounders that might mimic imprinting. Without heterogeneity, PP had more imprinting-detecting power than DRF. PP's power increased when parental affectedness status was ignored, but decreased with heterogeneity. With heterogeneity, type 1 error increased dramatically for both methods. However, DRF's power also increased under heterogeneity, more than was attributable to inflated type 1 error. Sex-specific penetrance could increase false positives for PP but not for DRF. False positives did not increase on ascertainment through an affected "mother". For PP, non-penetrant individuals increased information, arguing against using affected-only methods. The high type 1 error levels under some circumstances means these methods must be used cautiously. PMID:20374235

  3. Effect modification by time-varying covariates.

    PubMed

    Robins, James M; Hernán, Miguel A; Rotnitzky, Andrea

    2007-11-01

    Marginal structural models (MSMs) allow estimation of effect modification by baseline covariates, but they are less useful for estimating effect modification by evolving time-varying covariates. Rather, structural nested models (SNMs) were specifically designed to estimate effect modification by time-varying covariates. In their paper, Petersen et al. (Am J Epidemiol 2007;166:985-993) describe history-adjusted MSMs as a generalized form of MSM and argue that history-adjusted MSMs allow a researcher to easily estimate effect modification by time-varying covariates. However, history-adjusted MSMs can result in logically incompatible parameter estimates and hence in contradictory substantive conclusions. Here the authors propose a more restrictive definition of history-adjusted MSMs than the one provided by Petersen et al. and compare the advantages and disadvantages of using history-adjusted MSMs, as opposed to SNMs, to examine effect modification by time-dependent covariates. PMID:17875581

  4. Removing the influence of feature repetitions on the congruency sequence effect: why regressing out confounds from a nested design will often fall short.

    PubMed

    Schmidt, James R; De Schryver, Maarten; Weissman, Daniel H

    2014-12-01

    This article illustrates a shortcoming of using regression to control for confounds in nested designs. As an example, we consider the congruency sequence effect, which is the observation that the congruency effect in distractor interference (e.g., Stroop) tasks is smaller following incongruent as compared with congruent trials. The congruency sequence effect is often interpreted as indexing conflict adaptation: a relative increase of attention to the target following incongruent trials. However, feature repetitions across consecutive trials can complicate this interpretation. To control for this confound, the standard procedure is to delete all trials with a stimulus or response repetition and analyze the remaining trials. Notebaert and Verguts (2007) present an alternative method that allows researchers to use all trials. Specifically, they employ multiple regression to model conflict adaptation independent of feature repetitions. We show here that this approach fails to account for certain feature repetition effects. Furthermore, modeling these additional effects is typically not possible because of an upper bound on the number of degrees of freedom in the experiment. These findings have important implications for future investigations of conflict adaptation and, more broadly, for all researchers who attempt to regress out confounds in nested designs. PMID:25419672

  5. Does environmental confounding mask pleiotropic effects of a multiple sclerosis susceptibility variant on vitamin D in psychosis?

    PubMed Central

    Iyegbe, Conrad O; Acharya, Anita; Lally, John; Gardner-Sood, Poonam; Smith, Louise S; Smith, Shubulade; Murray, Robin; Howes, Oliver; Gaughran, Fiona

    2015-01-01

    Background: This work addresses the existing and emerging evidence of overlap within the environmental and genetic profiles of multiple sclerosis (MS) and schizophrenia. Aims: To investigate whether a genetic risk factor for MS (rs703842), whose variation is indicative of vitamin D status in the disorder, could also be a determinant of vitamin D status in chronic psychosis patients. Methods: A cohort of 224 chronic psychosis cases was phenotyped and biologically profiled. The relationship between rs703842 and physiological vitamin D status in the blood plasma was assessed by logistic regression. Deficiency was defined as a blood plasma concentration below 10 ng/µl. Potential environmental confounders of the vitamin D status were considered as part of the analysis. Results: We report suggestive evidence of an association with vitamin D status in established psychosis (ßstandardized=0.51, P=0.04). The logistic model fit significantly benefited from controlling for body mass index, depression and ethnicity (χ2=91.7; 2 degrees of freedom (df); P=1.2×1020). Conclusions: The results suggest that, in addition to lifestyle changes that accompany the onset of illness, vitamin D dysregulation in psychosis has a genetic component that links into MS. Further, comprehensive studies are needed to evaluate this prospect. PMID:27336042

  6. Structural equation modeling versus marginal structural modeling for assessing mediation in the presence of posttreatment confounding.

    PubMed

    Moerkerke, Beatrijs; Loeys, Tom; Vansteelandt, Stijn

    2015-06-01

    Inverse probability weighting for marginal structural models has been suggested as a strategy to estimate the direct effect of a treatment or exposure on an outcome in studies where the effect of mediator on outcome is subject to posttreatment confounding. This type of confounding, whereby confounders of the effect of mediator on outcome are themselves affected by the exposure, complicates mediation analyses and necessitates apt analysis strategies. In this article, we contrast the inverse probability weighting approach with the traditional path analysis approach to mediation analysis. We show that in a particular class of linear models, adjustment for posttreatment confounding can be realized via a fairly standard modification of the traditional path analysis approach. The resulting approach is simpler; by avoiding inverse probability weighting, it moreover results in direct effect estimators with smaller finite sample bias and greater precision. We further show that a particular variant of the G-estimation approach from the causal inference literature is equivalent with the path analysis approach in simple linear settings but is more generally applicable in settings with interactions and/or noncontinuous mediators and confounders. We conclude that the use of inverse probability weighting for marginal structural models to adjust for posttreatment confounding in mediation analysis is primarily indicated in nonlinear models for the outcome. PMID:25751514

  7. 'Bigger data' on scale-dependent effects of invasive species on biodiversity cannot overcome confounded analyses: a comment on Stohlgren & Rejmánek (2014).

    PubMed

    Chase, Jonathan M; Powell, Kristin I; Knight, Tiffany M

    2015-08-01

    A recent study by Stohlgren & Rejmánek (SR: Stohlgren TJ, Rejmánek M. 2014 Biol. Lett. 10. (doi:10.1098/rsbl.2013.0939)) purported to test the generality of a recent finding of scale-dependent effects of invasive plants on native diversity; dominant invasive plants decreased the intercept and increased the slope of the species-area relationship. SR (2014) find little correlation between invasive species cover and the slopes and intercepts of SARs across a diversity of sites. We show that the analyses of SR (2014) are inappropriate because of confounding causality. PMID:26246332

  8. An indicator for effects of organic toxicants on lotic invertebrate communities: Independence of confounding environmental factors over an extensive river continuum.

    PubMed

    Beketov, Mikhail A; Liess, Matthias

    2008-12-01

    Distinguishing between effects of natural and anthropogenic environmental factors on ecosystems is a fundamental problem in environmental science. In river systems the longitudinal gradient of environmental factors is one of the most relevant sources of dissimilarity between communities that could be confounded with anthropogenic disturbances. To test the hypothesis that in macroinvertebrate communities the distribution of species' sensitivity to organic toxicants is independent of natural longitudinal factors, but depends on contamination with organic toxicants, we analysed the relationship between community sensitivity SPEAR(organic) (average community sensitivity to organic toxicants) and natural and anthropogenic environmental factors in a large-scale river system, from alpine streams to a lowland river. The results show that SPEAR(organic) is largely independent of natural longitudinal factors, but strongly dependent on contamination with organic toxicants (petrochemicals and synthetic surfactants). Usage of SPEAR(organic) as a stressor-specific longitude-independent measure will facilitate detection of community disturbance by organic toxicants. PMID:18547697

  9. An empirical comparison of several clustered data approaches under confounding due to cluster effects in the analysis of complications of coronary angioplasty.

    PubMed

    Berlin, J A; Kimmel, S E; Ten Have, T R; Sammel, M D

    1999-06-01

    In the analysis of binary response data from many types of large studies, the data are likely to have arisen from multiple centers, resulting in a within-center correlation for the response. Such correlation, or clustering, occurs when outcomes within centers tend to be more similar to each other than to outcomes in other centers. In studies where there is also variability among centers with respect to the exposure of interest, analysis of the exposure-outcome association may be confounded, even after accounting for within-center correlations. We apply several analytic methods to compare the risk of major complications associated with two strategies, staged and combined procedures, for performing percutaneous transluminal coronary angioplasty (PTCA), a mechanical means of relieving blockage of blood vessels due to atherosclerosis. Combined procedures are used in some centers as a cost-cutting strategy. We performed a number of population-averaged and cluster-specific (conditional) analyses, which (a) make no adjustments for center effects of any kind; (b) make adjustments for the effect of center on only the response; or (c) make adjustments for both the effect of center on the response and the relationship between center and exposure. The method used for this third approach decomposes the procedure type variable into within-center and among-center components, resulting in two odds ratio estimates. The naive analysis, ignoring clusters, gave a highly significant effect of procedure type (OR = 1.6). Population average models gave marginally to very nonsignificant estimates of the OR for treatment type ranging from 1.6 to 1.2 with adjustment only for the effect of centers on response. These results depended on the assumed correlation structure. Conditional (cluster-specific) models and other methods that decomposed the treatment type variable into among- and within-center components all found no within-center effect of procedure type (OR = 1.02, consistently) and a

  10. The confounding effects of source isotopic heterogeneity on consumer-diet and tissue-tissue stable isotope relationships.

    PubMed

    Codron, Daryl; Sponheimer, Matt; Codron, Jacqui; Newton, Ian; Lanham, John L; Clauss, Marcus

    2012-08-01

    Stable isotope analysis of consumer tissues document patterns of resource use because data are linearly related to isotope compositions of their source(s) (i.e., food, water, etc.). Deviations in parameters estimated for these relationships can arise from variations in consumer tissue-diet spacing (Δ(TS)) and the level of isotopic heterogeneity in the source(s). We present a set of simple hypotheses that distinguish between the effects of Δ(TS) and source isotope heterogeneity. The latter may arise via mixed diets, during tissue turnover, or by isotopic routing of dietary components. We apply these concepts to stable carbon and nitrogen isotope relationships between gut contents and body tissues of large mammal herbivores from mixed C(3)/C(4) South African savannas and test predictions based on the compound- and/or time-specific data archived within each material. Predicted effects of source isotope heterogeneity are readily detected in carbon isotope relationships between materials representing different time periods or comprising bulk versus protein-only diet components. Differences in Δ(TS) of carbon isotopes across mammal herbivore species with very different feeding niches (and diet isotope compositions) are likely to be small or non-existent in these habitats. Variations in Δ(TS) estimated for nitrogen isotopes are much greater, leading to inconsistencies that cannot be explained by diet or trophic level effects alone. The effects of source heterogeneity on isotopic relationships generate numerical artefacts that have been misinterpreted as variations in Δ(TS). We caution against generalized application of hypotheses based on assumptions of source isotopic homogeneity, even for single diets commonly used in laboratory studies. More careful consideration of how heterogeneity affects consumer-diet relationships is needed for many field and laboratory systems. PMID:22349754

  11. Analysis of the effects of microbiome-related confounding factors on the reproducibility of the volatolomic test.

    PubMed

    Leja, Marcis; Amal, Haitham; Lasina, Ieva; Skapars, Roberts; Sivins, Armands; Ancans, Guntis; Tolmanis, Ivars; Vanags, Aigars; Kupcinskas, Juozas; Ramonaite, Rima; Khatib, Salam; Bdarneh, Shifaa; Natour, Rasha; Ashkar, Areen; Haick, Hossam

    2016-01-01

    Volatile organic compound (VOC) testing in breath has potential in gastric cancer (GC) detection. Our objective was to assess the reproducibility of VOCs in GC, and the effects of conditions modifying gut microbiome on the test results. Ten patients with GC were sampled for VOC over three consecutive days; 17 patients were sampled before and after H. pylori eradication therapy combined with a yeast probiotic; 61 patients were sampled before and after bowel cleansing (interventions affecting the microbiome). The samples were analyzed by: (1) gas chromatography linked to mass spectrometry (GC-MS), applying the non-parametric Wilcoxon test (level of significance p  <  0.05); (2) by cross-reactive nanoarrays combined with pattern recognition. Discriminant function analysis (DFA) was used to build the classification models; and leave-one-out cross-validation analysis was used to classify the findings. Exhaled VOCs profiles were stable for GC patients over a three day period. Alpha pinene (p  =  0.028) and ethyl acetate (p  =  0.030) increased after the antibiotic containing eradication regimen; acetone (p  =  0.0001) increased following bowel cleansing prior to colonoscopy. We further hypothesize that S. boulardii given with the standard eradication regimen to re-establish the gut microbiome was the source for long-term ethyl acetate production. Differences between the initial and the follow-up sample were also revealed in the DFA analysis of the sensor data. VOC measurement results are well-reproducible in GC patients indicating a useful basis for potential disease diagnostics. However, interventions with a potential effect on the gut microbiome may have an effect upon the VOC results, and therefore should be considered for diagnostic accuracy. PMID:27341527

  12. The Table 2 Fallacy: Presenting and Interpreting Confounder and Modifier Coefficients

    PubMed Central

    Westreich, Daniel; Greenland, Sander

    2013-01-01

    It is common to present multiple adjusted effect estimates from a single model in a single table. For example, a table might show odds ratios for one or more exposures and also for several confounders from a single logistic regression. This can lead to mistaken interpretations of these estimates. We use causal diagrams to display the sources of the problems. Presentation of exposure and confounder effect estimates from a single model may lead to several interpretative difficulties, inviting confusion of direct-effect estimates with total-effect estimates for covariates in the model. These effect estimates may also be confounded even though the effect estimate for the main exposure is not confounded. Interpretation of these effect estimates is further complicated by heterogeneity (variation, modification) of the exposure effect measure across covariate levels. We offer suggestions to limit potential misunderstandings when multiple effect estimates are presented, including precise distinction between total and direct effect measures from a single model, and use of multiple models tailored to yield total-effect estimates for covariates. PMID:23371353

  13. Confounding effects of anesthesia on functional activation in rodent brain: a study of halothane and alpha-chloralose anesthesia.

    PubMed

    Austin, V C; Blamire, A M; Allers, K A; Sharp, T; Styles, P; Matthews, P M; Sibson, N R

    2005-01-01

    Functional magnetic resonance imaging (fMRI) in animal models provides a platform for more extensive investigation of drug effects and underlying physiological mechanisms than is possible in humans. However, it is usually necessary for the animal to be anesthetized. In this study, we have used a rat model of direct cortical stimulation to investigate the effects of anesthesia in rodent fMRI. Specifically, we have sought to answer two questions (i) what is the relationship between baseline neuronal activity and the BOLD response to stimulation under halothane anesthesia? And (ii) how does the BOLD response change after transferring from halothane to the commonly used anesthetic alpha-chloralose? In the first set of experiments, we found no significant differences in the amplitude of the BOLD response at the different halothane doses studied, despite electroencephalography (EEG) recordings indicating a dose-dependent reduction in baseline neuronal activity with increasing halothane levels. In the second set of experiments, a reduction in the spatial extent of the BOLD response was apparent immediately after transfer from halothane to alpha-chloralose anesthesia, although no change in the peak signal change was evident. However, several hours after transfer to alpha-chloralose, a significant increase in both the spatial extent and peak height of the BOLD response was observed, as well as an increased sensitivity to secondary cortical and subcortical activation. These findings suggest that, although alpha-chloralose anesthesia is associated with a greater BOLD response for a fixed stimulus relative to halothane, there is substantial variation in the extent and magnitude of the response over time that could introduce considerable variability in studies using this anesthetic. PMID:15588600

  14. Estimating controlled direct effects in the presence of intermediate confounding of the mediator-outcome relationship: Comparison of five different methods.

    PubMed

    Lepage, B; Dedieu, D; Savy, N; Lang, T

    2016-04-01

    In mediation analysis between an exposure X and an outcome Y, estimation of the direct effect of X on Y by usual regression after adjustment for the mediator M may be biased if Z is a confounder between M and Y, and is also affected by X Alternative methods have been described to avoid such a bias: inverse probability of treatment weighting with and without weight truncation, the sequential g-estimator and g-computation. Our aim was to compare the usual linear regression adjusted for M to these methods when estimating the controlled direct effect between X and Y in the causal structure and to explore the size of the potential bias. Estimations were computed in several simulated data sets as well as real data. We observed an increased bias of the controlled direct effect estimation using linear regression adjusted for M for larger effects of X on M and larger effects of Z on M The sequential g-estimator and g-computation gave unbiased estimations with adequate coverage values in every situation studied. With continuous exposure X and mediator M, inverse probability of treatment weighting resulted in some bias and less satisfactory coverage for large effects of X on M and Z on M. PMID:23070596

  15. Confounding compression: the effects of posture, sizing and garment type on measured interface pressure in sports compression clothing.

    PubMed

    Brophy-Williams, Ned; Driller, Matthew William; Shing, Cecilia Mary; Fell, James William; Halson, Shona Leigh; Halson, Shona Louise

    2015-01-01

    The purpose of this investigation was to measure the interface pressure exerted by lower body sports compression garments, in order to assess the effect of garment type, size and posture in athletes. Twelve national-level boxers were fitted with sports compression garments (tights and leggings), each in three different sizes (undersized, recommended size and oversized). Interface pressure was assessed across six landmarks on the lower limb (ranging from medial malleolus to upper thigh) as athletes assumed sitting, standing and supine postures. Sports compression leggings exerted a significantly higher mean pressure than sports compression tights (P < 0.001). Oversized tights applied significantly less pressure than manufacturer-recommended size or undersized tights (P < 0.001), yet no significant differences were apparent between different-sized leggings. Standing posture resulted in significantly higher mean pressure application than a seated posture for both tights and leggings (P < 0.001 and P = 0.002, respectively). Pressure was different across landmarks, with analyses revealing a pressure profile that was neither strictly graduated nor progressive in nature. The pressure applied by sports compression garments is significantly affected by garment type, size and posture assumed by the wearer. PMID:25530213

  16. Interpretational Confounding or Confounded Interpretations of Causal Indicators?

    PubMed Central

    Bainter, Sierra A.; Bollen, Kenneth A.

    2014-01-01

    In measurement theory causal indicators are controversial and little-understood. Methodological disagreement concerning causal indicators has centered on the question of whether causal indicators are inherently sensitive to interpretational confounding, which occurs when the empirical meaning of a latent construct departs from the meaning intended by a researcher. This article questions the validity of evidence used to claim that causal indicators are inherently susceptible to interpretational confounding. Further, a simulation study demonstrates that causal indicator coefficients are stable across correctly-specified models. Determining the suitability of causal indicators has implications for the way we conceptualize measurement and build and evaluate measurement models. PMID:25530730

  17. P-wave indices in patients with pulmonary emphysema: do P-terminal force and interatrial block have confounding effects?

    PubMed Central

    Chhabra, Lovely; Chaubey, Vinod K; Kothagundla, Chandrasekhar; Bajaj, Rishi; Kaul, Sudesh; Spodick, David H

    2013-01-01

    Introduction Pulmonary emphysema causes several electrocardiogram changes, and one of the most common and well known is on the frontal P-wave axis. P-axis verticalization (P-axis > 60°) serves as a quasidiagnostic indicator of emphysema. The correlation of P-axis verticalization with the radiological severity of emphysema and severity of chronic obstructive lung function have been previously investigated and well described in the literature. However, the correlation of P-axis verticalization in emphysema with other P-indices like P-terminal force in V1 (Ptf), amplitude of initial positive component of P-waves in V1 (i-PV1), and interatrial block (IAB) have not been well studied. Our current study was undertaken to investigate the effects of emphysema on these P-wave indices in correlation with the verticalization of the P-vector. Materials and methods Unselected, routinely recorded electrocardiograms of 170 hospitalized emphysema patients were studied. Significant Ptf (s-Ptf) was considered ≥40 mm.ms and was divided into two types based on the morphology of P-waves in V1: either a totally negative (−) P wave in V1 or a biphasic (+/−) P wave in V1. Results s-Ptf correlated better with vertical P-vectors than nonvertical P-vectors (P = 0.03). s-Ptf also significantly correlated with IAB (P = 0.001); however, IAB and P-vector verticalization did not appear to have any significant correlation (P = 0.23). There was a very weak correlation between i-PV1 and frontal P-vector (r = 0.15; P = 0.047); however, no significant correlation was found between i-PV1 and P-amplitude in lead III (r = 0.07; P = 0.36). Conclusion We conclude that increased P-tf in emphysema may be due to downward right atrial position caused by right atrial displacement, and thus the common assumption that increased P-tf implies left atrial enlargement should be made with caution in patients with emphysema. Also, the lack of strong correlation between i-PV1 and P-amplitude in lead III or

  18. Interpretational Confounding or Confounded Interpretations of Causal Indicators?

    ERIC Educational Resources Information Center

    Bainter, Sierra A.; Bollen, Kenneth A.

    2014-01-01

    In measurement theory, causal indicators are controversial and little understood. Methodological disagreement concerning causal indicators has centered on the question of whether causal indicators are inherently sensitive to interpretational confounding, which occurs when the empirical meaning of a latent construct departs from the meaning…

  19. Assessing Sensitivity to Unmeasured Confounding Using a Simulated Potential Confounder

    ERIC Educational Resources Information Center

    Carnegie, Nicole Bohme; Harada, Masataka; Hill, Jennifer L.

    2016-01-01

    A major obstacle to developing evidenced-based policy is the difficulty of implementing randomized experiments to answer all causal questions of interest. When using a nonexperimental study, it is critical to assess how much the results could be affected by unmeasured confounding. We present a set of graphical and numeric tools to explore the…

  20. Adjusting for confounding effects of treatment switching in a randomized phase II study of dabrafenib plus trametinib in BRAF V600+ metastatic melanoma.

    PubMed

    Latimer, Nicholas R; Amonkar, Mayur M; Stapelkamp, Ceilidh; Sun, Peng

    2015-12-01

    Patients with BRAF V600E mutation-positive melanoma who were assigned to 150 mg dabrafenib twice daily combined with 2 mg trametinib once daily in a phase I/II study showed a median overall survival (OS) of 23.8 months, compared with 20.2 months for patients assigned to dabrafenib alone [hazard ratio (HR)=0.73, 95% confidence interval (CI) 0.43-1.24; data cutoff March 2013], on the basis of an intention-to-treat analysis. Because patients assigned to dabrafenib monotherapy were allowed to switch to combination therapy upon disease progression, we attempted to adjust for confounding effects on OS. Randomization-based adjustment methods, Rank Preserving Structural Failure Time Models and the Iterative Parameter Estimation algorithm, were used. Two analyses, 'treatment group' (assumes that treatment effect continues beyond treatment discontinuation) and 'on treatment' (assumes that the treatment effect disappears upon treatment discontinuation), were used to test assumptions on the durability of the treatment effect. A total of 45/54 (83%) patients assigned to dabrafenib monotherapy switched to the trametinib/dabrafenib combination. Adjusted OS HRs ranged from 0.47 to 0.50, depending on the analysis, compared with the unadjusted OS HR of 0.73. CIs continued to cross 1.00; thus, adjusted estimates did not provide statistically significant evidence of a treatment benefit on survival. Reduction of HRs after adjusting for the effect of treatment switching suggests that the intention-to-treat analysis underestimates the effect of dabrafenib plus trametinib on OS, although several factors, such as small trial size and methodological assumptions, affect the certainty of the conclusions. PMID:26340744

  1. Observed effects of “distributional learning” may not relate to the number of peaks. A test of “dispersion” as a confounding factor

    PubMed Central

    Wanrooij, Karin; Boersma, Paul; Benders, Titia

    2015-01-01

    Distributional learning of speech sounds is learning from simply being exposed to frequency distributions of speech sounds in one’s surroundings. In laboratory settings, the mechanism has been reported to be discernible already after a few minutes of exposure, in both infants and adults. These “effects of distributional training” have traditionally been attributed to the difference in the number of peaks between the experimental distribution (two peaks) and the control distribution (one or zero peaks). However, none of the earlier studies fully excluded a possibly confounding effect of the dispersion in the distributions. Additionally, some studies with a non-speech control condition did not control for a possible difference between processing speech and non-speech. The current study presents an experiment that corrects both imperfections. Spanish listeners were exposed to either a bimodal distribution encompassing the Dutch contrast /ɑ/∼/a/ or a unimodal distribution with the same dispersion. Before and after training, their accuracy of categorization of [ɑ]- and [a]-tokens was measured. A traditionally calculated p-value showed no significant difference in categorization improvement between bimodally and unimodally trained participants. Because of this null result, a Bayesian method was used to assess the odds in favor of the null hypothesis. Four different Bayes factors, each calculated on a different belief in the truth value of previously found effect sizes, indicated the absence of a difference between bimodally and unimodally trained participants. The implication is that “effects of distributional training” observed in the lab are not induced by the number of peaks in the distributions. PMID:26441719

  2. Modeling confounding by half-sibling regression.

    PubMed

    Schölkopf, Bernhard; Hogg, David W; Wang, Dun; Foreman-Mackey, Daniel; Janzing, Dominik; Simon-Gabriel, Carl-Johann; Peters, Jonas

    2016-07-01

    We describe a method for removing the effect of confounders to reconstruct a latent quantity of interest. The method, referred to as "half-sibling regression," is inspired by recent work in causal inference using additive noise models. We provide a theoretical justification, discussing both independent and identically distributed as well as time series data, respectively, and illustrate the potential of the method in a challenging astronomy application. PMID:27382154

  3. Modeling confounding by half-sibling regression

    PubMed Central

    Schölkopf, Bernhard; Hogg, David W.; Wang, Dun; Foreman-Mackey, Daniel; Janzing, Dominik; Simon-Gabriel, Carl-Johann; Peters, Jonas

    2016-01-01

    We describe a method for removing the effect of confounders to reconstruct a latent quantity of interest. The method, referred to as “half-sibling regression,” is inspired by recent work in causal inference using additive noise models. We provide a theoretical justification, discussing both independent and identically distributed as well as time series data, respectively, and illustrate the potential of the method in a challenging astronomy application. PMID:27382154

  4. Effect Modification and Interaction Terms: It Takes Two to Tango.

    PubMed

    Jupiter, Daniel C

    2016-01-01

    In this Investigators' Corner I look more deeply into the previously discussed phenomenon of effect modification. I revisit an explanation and examples of the phenomenon and then examine how to account for it statistically. Specifically, I show, in detail, how to write a regression equation that includes interaction terms that account for the effect modification. Finally, I look at interpretation of regression coefficients both with and without the presence of effect modification, and the associated interaction terms. PMID:27320193

  5. Effect of site-specific modification on restriction endonucleases and DNA modification methyltransferases.

    PubMed Central

    McClelland, M; Nelson, M; Raschke, E

    1994-01-01

    Restriction endonucleases have site-specific interactions with DNA that can often be inhibited by site-specific DNA methylation and other site-specific DNA modifications. However, such inhibition cannot generally be predicted. The empirically acquired data on these effects are tabulated for over 320 restriction endonucleases. In addition, a table of known site-specific DNA modification methyltransferases and their specificities is presented along with EMBL database accession numbers for cloned genes. PMID:7937074

  6. Xanthan gel system effective for profile modification

    SciTech Connect

    Burkholder, L.

    1985-04-15

    To cope with the problem of optimizing reservoir sweep efficiency, many companies today are utilizing a technique known as profile modification. This technique is based on the premise that a gelled polymer formulation can be injected into the reservoir some distance beyond the well bore where it creates a flow diversion. The successful application of profile modification techniques has resulted in significant increases in incremental oil recovery. The injectant is a xanthan-gum solution precross-linked with a chromium complex to form a gel. The polymer/chromium combination reduces permeability in the thief zones and diverts a higher percentage of the displacing fluids into previously unswept, oil-saturated portions of the reservoir. Although reservoir characteristics and brine composition are key considerations, xanthan/chrome gels can be tailored to meet almost any conditions. Fractures will require strong gels while tight formations, or formations with low parting pressures, will require thinner gels. Slug volume is designed to treat the ''thief'' interval and must be carefully sized to improve sweep efficiency within economical limits.

  7. The ACCE method: an approach for obtaining quantitative or qualitative estimates of residual confounding that includes unmeasured confounding

    PubMed Central

    Smith, Eric G.

    2015-01-01

    Background:  Nonrandomized studies typically cannot account for confounding from unmeasured factors.  Method:  A method is presented that exploits the recently-identified phenomenon of  “confounding amplification” to produce, in principle, a quantitative estimate of total residual confounding resulting from both measured and unmeasured factors.  Two nested propensity score models are constructed that differ only in the deliberate introduction of an additional variable(s) that substantially predicts treatment exposure.  Residual confounding is then estimated by dividing the change in treatment effect estimate between models by the degree of confounding amplification estimated to occur, adjusting for any association between the additional variable(s) and outcome. Results:  Several hypothetical examples are provided to illustrate how the method produces a quantitative estimate of residual confounding if the method’s requirements and assumptions are met.  Previously published data is used to illustrate that, whether or not the method routinely provides precise quantitative estimates of residual confounding, the method appears to produce a valuable qualitative estimate of the likely direction and general size of residual confounding. Limitations:  Uncertainties exist, including identifying the best approaches for: 1) predicting the amount of confounding amplification, 2) minimizing changes between the nested models unrelated to confounding amplification, 3) adjusting for the association of the introduced variable(s) with outcome, and 4) deriving confidence intervals for the method’s estimates (although bootstrapping is one plausible approach). Conclusions:  To this author’s knowledge, it has not been previously suggested that the phenomenon of confounding amplification, if such amplification is as predictable as suggested by a recent simulation, provides a logical basis for estimating total residual confounding. The method's basic approach is

  8. The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults

    PubMed Central

    Henson, Richard N. A.; Tyler, Lorraine K.; Davis, Simon W.; Shafto, Meredith A.; Taylor, Jason R.; Williams, Nitin; Cam‐CAN; Rowe, James B.

    2015-01-01

    Abstract In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood‐oxygenation level‐dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting‐state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath‐hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age‐related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population‐based Cambridge Centre for Ageing and Neuroscience cohort (Cam‐CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task‐based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects

  9. Radical cystectomy versus bladder preserving therapy for muscle-invasive urothelial carcinoma: examining confounding and misclassification bias in cancer observational comparative effectiveness research

    PubMed Central

    Bekelman, Justin E.; Handorf, Elizabeth A.; Guzzo, Thomas; Pollack, Craig Evan; Christodouleas, John; Resnick, Matthew J.; Swisher-McClure, Samuel; Vaughn, David; Have, Thomas Ten; Polsky, Daniel; Mitra, Nandita

    2013-01-01

    Objectives Radical cystectomy (RC) is the standard treatment for muscle-invasive Urothelial carcinoma of the bladder (UCB). Tri-modality bladder preserving therapy (BPT) is an alternative to RC, but randomized comparisons of RC versus BPT have proven infeasible. To compare RC versus BPT, we undertook an observational cohort study using registry and administrative claims data from the SEER-Medicare database. Methods We identified patients age 65 years or older diagnosed between 1995 and 2005 who received RC (n=1,426) or BPT (n=417). We examined confounding and stage misclassification in the comparison of RC and BPT using multivariable adjustment, propensity score-based adjustment, instrumental variable (IV) analysis and simulations. Results Patients who received BPT were older and more likely to have comorbid disease. After propensity score adjustment, BPT was associated with an increased hazard of death from any cause (HR 1.26; 95% CI, 1.05 – 1.53) and from bladder cancer (HR 1.31; 95% CI, 0.97 – 1.77). Using the local area cystectomy rate as an instrument, IV analysis demonstrated no differences in survival between BPT and RC (death from any cause HR 1.06; 95% CI, 0.78 – 1.31; death from bladder cancer HR 0.94; 95% CI, 0.55 – 1.18). Simulation studies for stage misclassification yielded results consistent with the IV analysis. Conclusions Survival estimates in an observational cohort of patients who underwent RC versus BPT differ by analytic method. Multivariable and propensity score adjustment revealed greater mortality associated with BPT relative to RC, while IV analysis and simulation studies suggest that the two treatments are associated with similar survival outcomes. PMID:23796296

  10. Disparity modifications and the emotional effects of stereoscopic images

    NASA Astrophysics Data System (ADS)

    Kawai, Takashi; Atsuta, Daiki; Tomiyama, Yuya; Kim, Sanghyun; Morikawa, Hiroyuki; Mitsuya, Reiko; Häkkinen, Jukka

    2014-03-01

    This paper describes a study that focuses on disparity changes in emotional scenes of stereoscopic (3D) images, in which an examination of the effects on pleasant and arousal was carried out by adding binocular disparity to 2D images that evoke specific emotions, and applying disparity modification based on the disparity analysis of famous 3D movies. From the results of the experiment, for pleasant, a significant difference was found only for the main effect of the emotions. On the other hand, for arousal, there was a trend of increasing the evaluation values in the order 2D condition, 3D condition and 3D condition applied the disparity modification for happiness, surprise, and fear. This suggests the possibility that binocular disparity and the modification affect arousal.

  11. Protective effects in radiation modification of elastomers

    NASA Astrophysics Data System (ADS)

    Głuszewski, Wojciech; Zagórski, Zbigniew P.; Rajkiewicz, Maria

    2014-12-01

    Saturated character of ethylene/octene thermoplastic elastomers demands an application of nonconventional methods of crosslinking connections between chains of molecules. These are organic peroxides, usually in the presence of coagents or an application of ionizing radiation. Several approaches (radiation, peroxide, peroxide/plus radiation and radiation/plus peroxide) were applied in crosslinking of elastomere Engage 8200. Attention was directed to the protection effects by aromatic peroxides and by photo- and thermostabilizers on radiolysis of elastomers. Role of dose of radiation, dose rate of radiation as well as the role of composition of elastomere on the radiation yield of hydrogen and absorbtion of oxygen was investigated. DRS method was used to follow postirradiation degradation. Influence of crosslinking methods on properties of elastomers is described. Results were interpreted from the point of view of protective actions of aromatic compounds.

  12. Effective Remediation of Reading Skills Using Behavior Modification.

    ERIC Educational Resources Information Center

    Rupley, William H.

    This study investigated the effectiveness of behavior modification techniques used in a 16-week summer remedial reading program for primary-level students. Ten elementary teachers enrolled in an introductory graduate course in diagnostic and remedial reading received eight hours of training in the use of behavior management techniques:…

  13. Methodological problems with population cancer studies: The forgotten confounding factors

    PubMed Central

    Blaylock, Russell L.

    2015-01-01

    Among clinical physicians it is the population study that is considered to be the “gold standard” of medical evidence concerning acceptable treatments. As new information comes to light concerning the many variables and confounding factors that can affect such studies, many older studies lose much of their original impact. While newer population studies take into consideration a far greater number of confounding factors many are still omitted and a number of these omitted factors can have profound effects on interpretation and validity of the study. In this editorial, I will discuss some of the omitted confounding factors and demonstrate how they can alter the interpretation of these papers and their clinical application. PMID:26097772

  14. Effects of aluminium surface morphology and chemical modification on wettability

    NASA Astrophysics Data System (ADS)

    Rahimi, M.; Fojan, P.; Gurevich, L.; Afshari, A.

    2014-03-01

    Aluminium alloys are some of the predominant metals in industrial applications such as production of heat exchangers, heat pumps. They have high heat conductivity coupled with a low specific weight. In cold working conditions, there is a risk of frost formation on the surface of aluminium in the presence of water vapour, which can lead to the deterioration of equipment performance. This work addresses the methods of surface modification of aluminium and their effect of the underlying surface morphology and wettability, which are the important parameters for frost formation. Three groups of real-life aluminium surfaces of different morphology: unpolished aluminium, polished aluminium, and aluminium foil, were subjected to surface modification procedures which involved the formation of a layer of hydrophilic hyperbranched polyethyleneglycol via in situ polymerization, molecular vapour deposition of a monolayer of fluorinated silane, and a combination of those. The effect of these surface modification techniques on roughness and wettability of the aluminium surfaces was elucidated by ellipsometry, contact angle measurements and atomic force microscopy. We demonstrated that by employing different types of surface modifications the contact angle of water droplets on aluminium samples can be varied from 12° to more than 120°. A crossover from Cassie-Baxter to Wenzel regime upon changing the surface roughness was also observed.

  15. The fallacy of Ratio Correction to address confounding factors

    PubMed Central

    Karp, Natasha A; Segonds-Pichon, Anne; Gerdin, Anna-Karin B; Ramírez-Solis, Ramiro; White, Jacqueline K

    2014-01-01

    Scientists aspire to measure cause and effect. Unfortunately confounding variables, ones that are associated with both the probable cause and the outcome, can lead to an association that is true but potentially misleading. For example, altered body weight is often observed in a gene knockout, however many other variables, such as lean mass, will also change as the body weight changes. This leaves the researcher asking whether the change in that variable is expected for that change in weight. Ratio Correction, which is often referred to as Normalization, is a method used commonly to remove the effect of a confounding variable. Although Ratio Correction is used widely in biological research, it is not the method recommended in the statistical literature to address confounding factors; instead regression methods such as the analysis of covariance (ANCOVA) are proposed. This method examines the difference in means after adjusting for the confounding relationship. Using real data, this manuscript demonstrates how the Ratio Correction approach is flawed and can result in erroneous calls of significance leading to inappropriate biological conclusions. This arises as some of the underlying assumptions are not met. The manuscript goes on to demonstrate that researchers should use ANCOVA, and discusses how graphical tools can be used readily to judge the robustness of this method. This study is therefore a clear example of why assumption testing is an important component of a study and thus why it is included in the Animal Research: reporting of In Vivo Experiment (ARRIVE) guidelines. PMID:22829707

  16. The importance of confounding in observational before-and-after studies of road safety measures.

    PubMed

    Elvik, Rune

    2002-09-01

    This paper discusses the importance of confounding in observational before-and-after studies of road safety measures. The importance of the approach taken to controlling for confounding factors is shown by means of examples. It is shown that the size of the effect on accidents attributed to a road safety measure can be profoundly affected by which confounding factors are controlled for in an evaluation study, and the way this is done. Simple before-and-after studies, not controlling for any confounding factors should never be trusted and are likely to overstate the effects of road safety measures. PMID:12214957

  17. Estimation of Indirect Effects in the Presence of Unmeasured Confounding for the Mediator-Outcome Relationship in a Multilevel 2-1-1 Mediation Model

    ERIC Educational Resources Information Center

    Talloen, Wouter; Moerkerke, Beatrijs; Loeys, Tom; De Naeghel, Jessie; Van Keer, Hilde; Vansteelandt, Stijn

    2016-01-01

    To assess the direct and indirect effect of an intervention, multilevel 2-1-1 studies with intervention randomized at the upper (class) level and mediator and outcome measured at the lower (student) level are frequently used in educational research. In such studies, the mediation process may flow through the student-level mediator (the within…

  18. Motivated attention: Incentive effects on attentional modification of prepulse inhibition

    PubMed Central

    Ashare, Rebecca L.; Hawk, Larry W.; Mazzullo, Rebecca J.

    2008-01-01

    Prepulse inhibition (PPI) of startle is greater for attended compared to ignored prestimuli, and, consistent with theories of motivated attention, initial evidence suggests that this effect is greater among participants given performance-based incentives. The present study examined a within-subjects incentive manipulation. Participants (n = 41) completed two blocks of a tone discrimination task. During the incentive block, participants received trialwise feedback with small monetary incentives for task performance. Startle eyeblink EMG responses to auditory probes were assessed at 60-, 120-, and 180-ms tone-probe stimulus onset asynchronies (SOAs). As predicted, PPI was enhanced during attended compared to ignored prestimuli only at the 120-ms SOA in the incentive condition. There was no evidence of attentional modification in the no-incentive condition. These data suggest that attentional modification of PPI is sensitive to within-subjects manipulations of incentive, providing a useful tool for testing models of motivated attention in psychopathology and psychopharmacology. PMID:17640265

  19. Ultrafast transient absorption spectrum of the room temperature Ionic liquid 1-hexyl-3-methylimidazolium bromide: Confounding effects of photo-degradation

    NASA Astrophysics Data System (ADS)

    Musat, Raluca M.; Crowell, Robert A.; Polyanskiy, Dmitriy E.; Thomas, Marie F.; Wishart, James F.; Katsumura, Yosuke; Takahashi, Kenji

    2015-12-01

    The photochemistry of the charge transfer (CT) band of the room temperature ionic liquid (RTIL) 1-hexyl-3-methylimidazolium bromide (HMIm+/Br-) is investigated using near-IR to vis ultrafast transient absorption (TA) and steady-state UV absorption spectroscopies. Continuous irradiation of the CT band at 266 nm results in the formation of photo-products that absorb strongly at 266 nm. It is shown that these photo-products, which are apparently very stable, adversely affect ultrafast TA measurements. Elimination of these effects reveals at least two transient species that exist within the TA detection window of 100 fs to 3 ns and 500-1250 nm. One of the components is a short-lived (<1 ps) species that absorbs at 1080 nm. The second band exhibits a multicomponent spectrum that is very broad with an absorption maximum around 600 nm and a lifetime that is longer than the 3 ns window of our TA spectrometer. Within the signal to noise ratio of the TA spectrometer little to no solvated electron is generated by the CT mechanism.

  20. Depression and termination of pregnancy (induced abortion) in a national cohort of young Australian women: the confounding effect of women's experience of violence

    PubMed Central

    Taft, Angela J; Watson, Lyndsey F

    2008-01-01

    .65). Linear regression showed a four fold greater effect of violence than termination or births. Conclusion Violence, especially partner violence, makes a significantly greater contribution to women's depression compared with pregnancy termination or births. Any strategy to reduce the burden of women's depression should include prevention or reduction of violence against women and strengthening women's sexual and reproductive health to ensure that pregnancies are planned and wanted. PMID:18302736

  1. Accuracy and the Effect of Possible Subject-Based Confounders of Magnitude-Based MRI for Estimating Hepatic Proton Density Fat Fraction in Adults, Using MR Spectroscopy as Reference

    PubMed Central

    Heba, Elhamy R.; Desai, Ajinkya; Zand, Kevin A.; Hamilton, Gavin; Wolfson, Tanya; Schlein, Alexandra N.; Gamst, Anthony; Loomba, Rohit; Sirlin, Claude B.; Middleton, Michael S.

    2016-01-01

    Purpose To determine the accuracy and the effect of possible subject-based confounders of magnitude-based magnetic resonance imaging (MRI) for estimating hepatic proton density fat fraction (PDFF) for different numbers of echoes in adults with known or suspected nonalcoholic fatty liver disease, using MR spectroscopy (MRS) as a reference. Materials and Methods In this retrospective analysis of 506 adults, hepatic PDFF was estimated by unenhanced 3.0T MRI, using right-lobe MRS as reference. Regions of interest placed on source images and on six-echo parametric PDFF maps were colocalized to MRS voxel location. Accuracy using different numbers of echoes was assessed by regression and Bland–Altman analysis; slope, intercept, average bias, and R2 were calculated. The effect of age, sex, and body mass index (BMI) on hepatic PDFF accuracy was investigated using multivariate linear regression analyses. Results MRI closely agreed with MRS for all tested methods. For three- to six-echo methods, slope, regression intercept, average bias, and R2 were 1.01–0.99, 0.11–0.62%, 0.24–0.56%, and 0.981–0.982, respectively. Slope was closest to unity for the five-echo method. The two-echo method was least accurate, underestimating PDFF by an average of 2.93%, compared to an average of 0.23–0.69% for the other methods. Statistically significant but clinically nonmeaningful effects on PDFF error were found for subject BMI (P range: 0.0016 to 0.0783), male sex (P range: 0.015 to 0.037), and no statistically significant effect was found for subject age (P range: 0.18–0.24). Conclusion Hepatic magnitude-based MRI PDFF estimates using three, four, five, and six echoes, and six-echo parametric maps are accurate compared to reference MRS values, and that accuracy is not meaningfully confounded by age, sex, or BMI. PMID:26201284

  2. A flexible, interpretable framework for assessing sensitivity to unmeasured confounding.

    PubMed

    Dorie, Vincent; Harada, Masataka; Carnegie, Nicole Bohme; Hill, Jennifer

    2016-09-10

    When estimating causal effects, unmeasured confounding and model misspecification are both potential sources of bias. We propose a method to simultaneously address both issues in the form of a semi-parametric sensitivity analysis. In particular, our approach incorporates Bayesian Additive Regression Trees into a two-parameter sensitivity analysis strategy that assesses sensitivity of posterior distributions of treatment effects to choices of sensitivity parameters. This results in an easily interpretable framework for testing for the impact of an unmeasured confounder that also limits the number of modeling assumptions. We evaluate our approach in a large-scale simulation setting and with high blood pressure data taken from the Third National Health and Nutrition Examination Survey. The model is implemented as open-source software, integrated into the treatSens package for the R statistical programming language. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID:27139250

  3. Structural confounding of area-level deprivation and segreation: an empirical example

    EPA Science Inventory

    The neighborhood effects literature has grown, but its utility is limited by the lack of attention paid to non-random selection into neighborhoods. Confounding occurs when an exposure and an outcome share an underlying common cause. Confounding resulting from differential allocat...

  4. Resting-state FMRI confounds and cleanup

    PubMed Central

    Murphy, Kevin; Birn, Rasmus M.; Bandettini, Peter A.

    2013-01-01

    The goal of resting-state functional magnetic resonance imaging (FMRI) is to investigate the brain’s functional connections by using the temporal similarity between blood oxygenation level dependent (BOLD) signals in different regions of the brain “at rest” as an indicator of synchronous neural activity. Since this measure relies on the temporal correlation of FMRI signal changes between different parts of the brain, any non-neural activity-related process that affects the signals will influence the measure of functional connectivity, yielding spurious results. To understand the sources of these resting-state FMRI confounds, this article describes the origins of the BOLD signal in terms of MR physics and cerebral physiology. Potential confounds arising from motion, cardiac and respiratory cycles, arterial CO2 concentration, blood pressure/cerebral autoregulation, and vasomotion are discussed. Two classes of techniques to remove confounds from resting-state BOLD time series are reviewed: 1) those utilising external recordings of physiology and 2) data-based cleanup methods that only use the resting-state FMRI data itself. Further methods that remove noise from functional connectivity measures at a group level are also discussed. For successful interpretation of resting-state FMRI comparisons and results, noise cleanup is an often over-looked but essential step in the analysis pipeline. PMID:23571418

  5. Air pollutants and health outcomes: Assessment of confounding by influenza

    NASA Astrophysics Data System (ADS)

    Thach, Thuan-Quoc; Wong, Chit-Ming; Chan, King-Pan; Chau, Yuen-Kwan; Neil Thomas, G.; Ou, Chun-Quan; Yang, Lin; Peiris, Joseph S. M.; Lam, Tai-Hing; Hedley, Anthony J.

    2010-04-01

    We assessed confounding of associations between short-term effects of air pollution and health outcomes by influenza using Hong Kong mortality and hospitalization data for 1996-2002. Three measures of influenza were defined: (i) intensity: weekly proportion of positive influenza viruses, (ii) epidemic: weekly number of positive influenza viruses ≥4% of the annual number for ≥2 consecutive weeks, and (iii) predominance: an epidemic period with co-circulation of respiratory syncytial virus <2% of the annual positive isolates for ≥2 consecutive weeks. We examined effects of influenza on associations between nitrogen dioxide (NO 2), sulfur dioxide (SO 2), particulate matter with aerodynamic diameter ≤10 μm (PM 10) and ozone (O 3) and health outcomes including all natural causes mortality, cardiorespiratory mortality and hospitalization. Generalized additive Poisson regression model with natural cubic splines was fitted to control for time-varying covariates to estimate air pollution health effects. Confounding with influenza was assessed using an absolute difference of >0.1% between unadjusted and adjusted excess risks (ER%). Without adjustment, pollutants were associated with positive ER% for all health outcomes except asthma and stroke hospitalization with SO 2 and stroke hospitalization with O 3. Following adjustment, changes in ER% for all pollutants were <0.1% for all natural causes mortality, but >0.1% for mortality from stroke with NO 2 and SO 2, cardiac or heart disease with NO 2, PM 10 and O 3, lower respiratory infections with NO 2 and O 3 and mortality from chronic obstructive pulmonary disease with all pollutants. Changes >0.1% were seen for acute respiratory disease hospitalization with NO 2, SO 2 and O 3 and acute lower respiratory infections hospitalization with PM 10. Generally, influenza does not confound the observed associations of air pollutants with all natural causes mortality and cardiovascular hospitalization, but for some pollutants

  6. Ecological Effects of Weather Modification: A Problem Analysis.

    ERIC Educational Resources Information Center

    Cooper, Charles F.; Jolly, William C.

    This publication reviews the potential hazards to the environment of weather modification techniques as they eventually become capable of producing large scale weather pattern modifications. Such weather modifications could result in ecological changes which would generally require several years to be fully evident, including the alteration of…

  7. Modifications to ideal stability by kinetic effects in NSTX

    NASA Astrophysics Data System (ADS)

    Berkery, J. W.; Sabbagh, S. A.; Bell, R. E.; Gerhardt, S. P.; LeBlanc, B. P.; Menard, J. E.

    2015-11-01

    Marginal stability points of global modes during high plasma pressure operation in the National Spherical Torus Experiment (NSTX) device can be found by computing kinetic modifications to ideal magnetohydrodynamic limits on stability. Calculations with the DCON code for nearly five thousand experimental equilibria show that previous estimates of the no-wall limit (below which the ideal kink/ballooning mode would be stable even without conducting structure surrounding the plasma) on the plasma beta (a ratio of plasma pressure to magnetic pressure) and internal inductance (a measure of the current profile peakedness) were relatively accurate, though about 10% low. The no-wall beta limit also decreased with increasing aspect ratio and increasing broadness of the pressure profile, and these dependencies have implications for the upgrade to NSTX which has a larger aspect ratio and new neutral beams that may increase the broadness of pressure and current profiles. Kinetic modifications to ideal limits calculated with the Modifications to Ideal Stability by Kinetic effects (MISK) code are further validated by detailed comparison with experimental results from NSTX. In several discharges the code predicts a transition from damping of the mode to growth as the time approaches the experimental time of marginal stability to the resistive wall mode (RWM). The main stabilization mechanism is through rotational resonances with the motions of thermal particles in the plasma, though energetic particles also contribute to stability, and it is often when the plasma rotation falls in between these resonances that the RWM was destabilized in NSTX. The calculations are found to be slightly affected by changing the assumed magnetic structure of the mode as well. These validations are important for real-time assessment of stability limits for disruption avoidance, and reliable projections of the stability of future devices.

  8. Systematically missing confounders in individual participant data meta-analysis of observational cohort studies.

    PubMed

    Jackson, Dan; White, Ian; Kostis, J B; Wilson, A C; Folsom, A R; Wu, K; Chambless, L; Benderly, M; Goldbourt, U; Willeit, J; Kiechl, S; Yarnell, J W G; Sweetnam, P M; Elwood, P C; Cushman, M; Psaty, B M; Tracy, R P; Tybjaerg-Hansen, A; Haverkate, F; de Maat, M P M; Thompson, S G; Fowkes, F G R; Lee, A J; Smith, F B; Salomaa, V; Harald, K; Rasi, V; Vahtera, E; Jousilahti, P; D'Agostino, R; Kannel, W B; Wilson, P W F; Tofler, G; Levy, D; Marchioli, R; Valagussa, F; Rosengren, A; Wilhelmsen, L; Lappas, G; Eriksson, H; Cremer, P; Nagel, D; Curb, J D; Rodriguez, B; Yano, K; Salonen, J T; Nyyssönen, K; Tuomainen, T-P; Hedblad, B; Engström, G; Berglund, G; Loewel, H; Koenig, W; Hense, H W; Meade, T W; Cooper, J A; De Stavola, B; Knottenbelt, C; Miller, G J; Cooper, J A; Bauer, K A; Rosenberg, R D; Sato, S; Kitamura, A; Naito, Y; Iso, H; Salomaa, V; Harald, K; Rasi, V; Vahtera, E; Jousilahti, P; Palosuo, T; Ducimetiere, P; Amouyel, P; Arveiler, D; Evans, A E; Ferrieres, J; Juhan-Vague, I; Bingham, A; Schulte, H; Assmann, G; Cantin, B; Lamarche, B; Despres, J-P; Dagenais, G R; Tunstall-Pedoe, H; Lowe, G D O; Woodward, M; Ben-Shlomo, Y; Davey Smith, G; Palmieri, V; Yeh, J L; Meade, T W; Rudnicka, A; Brennan, P; Knottenbelt, C; Cooper, J A; Ridker, P; Rodeghiero, F; Tosetto, A; Shepherd, J; Lowe, G D O; Ford, I; Robertson, M; Brunner, E; Shipley, M; Feskens, E J M; Di Angelantonio, E; Kaptoge, S; Lewington, S; Lowe, G D O; Sarwar, N; Thompson, S G; Walker, M; Watson, S; White, I R; Wood, A M; Danesh, J

    2009-04-15

    One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohorts PMID:19222087

  9. Modifications of the Schwarzschild null geodesics in effective field theories

    SciTech Connect

    Ahmadi, N.

    2009-12-15

    In this paper the dynamics of Schwarzschild null geodesics in the context of low-energy effective field theories incorporating some interactions violating the equivalence principle is examined. Nonperturbed geodesics are expressed in terms of a convenient set of constants called orbital elements. The modifications introduced by the effective interactions are treated as small perturbations, then the method of variation of parameters is employed to find the evolution of the orbital elements for the true worldlines. We next focus our discussion on the geometry of nondispersive photon orbits and highlight the importance of different orbital elements in long-term change of the orbit. This calculation shows that nondispersive forces acting on null geodesics drive a secular growth of the positional elements. As an application of our results we examine the evolution of mean orbital elements in the semiclassical theory of quantum gravitational optics and show that the averaged correction terms are within the range of the uncertainty principle.

  10. Effect of thermal modification on rheological properties of polyethylene blends

    SciTech Connect

    Siriprumpoonthum, Monchai; Nobukawa, Shogo; Yamaguchi, Masayuki; Satoh, Yasuo; Sasaki, Hiroko

    2014-03-15

    We examined the effects of thermal modification under flow field on the rheological properties of linear low-density polyethylene (LLDPE) with high molecular weight, low-density polyethylene (LDPE), and their blends, without thermal stabilizer. Although structural changes during processing are not detected by size extrusion chromatography or nuclear magnetic resonance spectroscopy, linear viscoelastic properties changed greatly, especially for the LLDPE. A cross-linking reaction took place, leading to, presumably, star-shaped long-chain branches. Consequently, the modified LLDPE, having high zero-shear viscosity, became a thermorheologically complex melt. Moreover, it should be noted that the drawdown force, defined as the uniaxial elongational force at a constant draw ratio, was significantly enhanced for the blends. Enhancement of elongational viscosity was also detected. The drawdown force and elongational viscosity are marked for the thermally modified blend as compared with those for the blend of thermally modified pure components. Intermolecular cross-linking reactions between LDPE and LLDPE, yielding polymers with more than two branch points per chain, result in marked strain-hardening in the elongational viscosity behavior even at small strain. The recovery curve of the oscillatory modulus after the shear modification is further evidence of a branched structure.

  11. Effects of lifestyle modification programs on cardiac risk factors.

    PubMed

    Razavi, Moaven; Fournier, Stephen; Shepard, Donald S; Ritter, Grant; Strickler, Gail K; Stason, William B

    2014-01-01

    Medicare conducted a payment demonstration to evaluate the effectiveness of two intensive lifestyle modification programs in patients with symptomatic coronary artery disease: the Dr. Dean Ornish Program for Reversing Heart Disease (Ornish) and Cardiac Wellness Program of the Benson-Henry Mind Body Institute. This report describes the changes in cardiac risk factors achieved by each program during the active intervention year and subsequent year of follow-up. The demonstration enrolled 580 participants who had had an acute myocardial infarction, had undergone coronary artery bypass graft surgery or percutaneous coronary intervention within 12 months, or had documented stable angina pectoris. Of these, 98% completed the intense 3-month intervention, 71% the 12-month intervention, and 56% an additional follow-up year. Most cardiac risk factors improved significantly during the intense intervention period in both programs. Favorable changes in cardiac risk factors and functional cardiac capacity were maintained or improved further at 12 and 24 months in participants with active follow-up. Multivariable regressions found that risk-factor improvements were positively associated with abnormal baseline values, Ornish program participation for body mass index and systolic blood pressure, and with coronary artery bypass graft surgery. Expressed levels of motivation to lose weight and maintain weight loss were significant independent predictors of sustained weight loss (p = 0.006). Both lifestyle modification programs achieved well-sustained reductions in cardiac risk factors. PMID:25490202

  12. [Bias and confounding: pharmacoepidemiological study using administrative database].

    PubMed

    Nojiri, Shuko

    2015-01-01

    The provision of health care frequently creates digitalized data such as hospital-based electronic data, medication prescription records, and claims data collectively termed "administrative database research". The data source and analytical opportunities for study create risks that can lead to misinterpretation or bias the results. This review serves as an introduction to the concept of bias and confounding to help researchers conduct methodologically sound pharmacoepidemiologic research projects using administrative databases. Beyond general considerations for observational study, there are several unique issues related to database research that should be addressed. The risks of uninterpretable or biased results can be minimized by: providing a robust description of the data tables used; focusing on why and how they were created; measuring and reporting the accuracy of diagnostic and procedural codes used; and properly accounting for any time-dependent nature of variables. The hallmark of good research is rigorously careful analysis and interpretation. The promise for value of real world evidence using databases in medical decision making must be balanced against concerns related to observational inherited limitations for bias and confounding. Researchers should aim to avoid bias in the design of a study, adjust for confounding, and discuss the effects of residual bias on the results. PMID:26028416

  13. PM2.5 and survival among older adults: Effect modification by particulate composition

    PubMed Central

    Kioumourtzoglou, Marianthi-Anna; Austin, Elena; Koutrakis, Petros; Dominici, Francesca; Schwartz, Joel; Zanobetti, Antonella

    2015-01-01

    Background Fine particulate (PM2.5) air pollution has been consistently linked to survival, but reported effect estimates are geographically heterogeneous. Exposure to different types of particle mixtures may explain some of this variation. Methods We used k-means cluster analyses to identify cities with similar pollution profiles, (i.e. PM2.5 composition) across the US. We examined the impact of PM2.5 on survival, and its variation across clusters of cities with similar PM2.5 composition, among Medicare enrollees in 81 US cities (2000–2010). We used time-varying annual PM2.5 averages, measured at ambient central monitoring sites, as the exposure of interest. We ran by-city Cox models, adjusting for individual data on previous cardiopulmonary-related hospitalizations and stratifying by follow-up time, age, gender and race. This eliminates confounding by factors varying across cities and long-term trends, focusing on year-to-year variations of air pollution around its city-specific mean and trend. We then pooled the city-specific effects using a random effects meta-regression. In this second stage, we also assessed effect modification by cluster membership and estimated cluster-specific PM2.5 effects. Results We followed more than 19 million subjects and observed more than 6 million deaths. We found a harmful impact of annual PM2.5 concentrations on survival (HR = 1.11 [95% confidence interval = 1.01–1.23] per 10 µg/m3). This effect was modified by particulate composition, with higher effects observed in clusters containing high concentrations of nickel, vanadium and sulfate. For instance, our highest effect estimate was observed in cities with harbors in the Northwest, characterized by high nickel, vanadium and elemental carbon concentrations (1.9 [1.1–3.3]). We observed null or negative associations in clusters with high oceanic and crustal particles. Conclusions To our knowledge, this is the first study to examine the association between PM2.5 composition

  14. Ceramic modifications of porous titanium: effects on macrophage activation.

    PubMed

    Scislowska-Czarnecka, A; Menaszek, E; Szaraniec, B; Kolaczkowska, E

    2012-12-01

    Porous titanium is one of the most widely used implant materials because of its mechanical properties, however, it is also characterised by low bioactivity. To improve the above parameter we prepared three modifications of the porous (30 wt%) titanium (Ti) surface by covering it with bioactive hydroxyapatite (HA), bioglass (BG) and calcium silicate (CS). Subsequently we tested the impact of the modifications on macrophages directing the inflammatory response that might compromise the implant bioactivity. In the study we investigated the in vitro effects of the materials on murine cell line RAW 264.7 macrophage adherence, morphology and activation (production/release of metalloproteinase MMP-9 and pro- and anti-inflammatory cytokines). CS Ti decreased the macrophage adherence and up-regulated the release of several pro-inflammatory mediators, including TNF-α, IL-6, IL-12. Also HA Ti reduced the cell adherence but other parameters were generally not increased, except of TNF-α. In contrast, BG Ti improved macrophage adherence and either decreased production of multiple mediators (MMP-9, TNF-α, IFN-γ, MCP-1) or did not change it in comparison to the porous titanium. We can conclude that analyzing the effects on the inflammatory response initiated by macrophages in vitro, calcium silicate did not improve the biological properties of the porous titanium. The improved bioactivity of titanium was, however, achieved by the application of the hydroxyapatite and bioglass layers. The present in vitro results suggest that these materials, HA Ti and especially BG Ti, may be suitable for in vivo application and thus justify their further investigation. PMID:22939219

  15. Effect of chemical modifications on allergenic potency of peanut proteins

    PubMed Central

    Bencharitiwong, Ramon; van der Kleij, Hanneke P.M.; Koppelman, Stef J.

    2015-01-01

    Background: Modification of native peanut extracts could reduce adverse effects of peanut immunotherapy. Objective: We sought to compare native and chemically modified crude peanut extract (CPE) and major peanut allergens Ara h 2 and Ara h 6 in a mediator-release assay based on the rat basophilic leukemia (RBL) cell line transfected with human Fcε receptor. Methods: Native Ara h 2/6 was reduced and alkylated (RA), with or without additional glutaraldehyde treatment (RAGA). CPE was reduced and alkylated. Sera of subjects with peanut allergy (16 males; median age 7 years) were used for overnight RBL-passive sensitization. Cells were stimulated with 0.1 pg/mL to 10 μg/mL of peanut. β-N-acetylhexosaminidase release (NHR) was used as a marker of RBL degranulation, expressed as a percentage of total degranulation caused by Triton X. Results: Median peanut-specific immunoglobulin E was 233 kUA/L. Nineteen subjects were responders, NHR ≥ 10% in the mediator release assay. Responders had reduced NHR by RA and RAGA compared with the native Ara h 2/6. Modification resulted in a later onset of activation by 10- to 100-fold in concentration and a lowering of the maximum release. Modified RA-Ara h 2/6 and RAGA-Ara h 2/6 caused significantly lower maximum mediator release than native Ara h 2/6, at protein concentrations 0.1, 1, and 10 ng/mL (p < 0.001, < 0.001, and < 0.001, respectively, for RA; and < 0.001, 0.026, and 0.041, respectively, for RAGA). RA-CPE caused significantly lower maximum NHR than native CPE, at protein concentration 1 ng/mL (p < 0.001) and 10 ng/mL (p < 0.002). Responders had high rAra h 2 immunoglobulin E (mean, 61.1 kUA/L; p < 0.001) and higher NHR in mediator release assay to native Ara h 2/6 than CPE, which indicates that Ara h 2/6 were the most relevant peanut allergens in these responders. Conclusions: Chemical modification of purified native Ara h 2 and Ara h 6 reduced mediator release in an in vitro assay ∼100-fold, which indicates decreased

  16. Ground cloud related weather modification effects. [heavy lift launch vehicles

    NASA Technical Reports Server (NTRS)

    Lee, J.

    1980-01-01

    The principal concerns about inadvertent weather modification by the solar power satellite system rocket effluents are discussed, namely the possibility that the ground cloud might temporarily modify local weather and the cumulative effects of nearly 500 launches per year. These issues are discussed through the consideration of (1) the possible alteration of the microphysical processes of clouds in the general area due to rocket effluents and debris and cooling water entrained during the launch and (2) the direct dynamical and thermodynamical responses to the inputs of thermal energy and moisture from the rocket exhaust for given ambient meteorological conditions. The huge amount of thermal energy contained in the exhaust of the proposed launch vehicle would in some situations induce a saturated, wet convective cloud or enhance an existing convective activity. Nevertheless, the effects would be limited to the general area of the launch site. The observed long lasting high concentrations of cloud condensation nuclei produced during and after a rocket launch may appreciably affect the frequency of occurrence and persistence of fogs and haze. In view of the high mission frequency proposed for the vehicle launches, a potential exists for a cumulative effect.

  17. Stability studies of plasma modification effects of polylactide and polycaprolactone surface layers

    NASA Astrophysics Data System (ADS)

    Moraczewski, Krzysztof; Stepczyńska, Magdalena; Malinowski, Rafał; Rytlewski, Piotr; Jagodziński, Bartłomiej; Żenkiewicz, Marian

    2016-07-01

    The article presents results of research on the stability of oxygen plasma modification effects of polylactide and polycaprolactone surface layers. The modified samples were aged for three, six or nine weeks. The studies were carried out using scanning electron microscopy, goniometry and Fourier transform infrared spectroscopy. Studies have shown that the plasma modification has significant impact on the geometric structure and chemical composition of the surface, wettability and surface energy of tested polymers. The modification effects are not permanent. It has been observed that over time the effects of plasma modification fade. Studies have shown that modifying effect lasts longer in the case of polycaprolactone.

  18. Confounded by sequencing depth in association studies of rare alleles.

    PubMed

    Garner, Chad

    2011-05-01

    Next-generation DNA sequencing technologies are facilitating large-scale association studies of rare genetic variants. The depth of the sequence read coverage is an important experimental variable in the next-generation technologies and it is a major determinant of the quality of genotype calls generated from sequence data. When case and control samples are sequenced separately or in different proportions across batches, they are unlikely to be matched on sequencing read depth and a differential misclassification of genotypes can result, causing confounding and an increased false-positive rate. Data from Pilot Study 3 of the 1000 Genomes project was used to demonstrate that a difference between the mean sequencing read depth of case and control samples can result in false-positive association for rare and uncommon variants, even when the mean coverage depth exceeds 30× in both groups. The degree of the confounding and inflation in the false-positive rate depended on the extent to which the mean depth was different in the case and control groups. A logistic regression model was used to test for association between case-control status and the cumulative number of alleles in a collapsed set of rare and uncommon variants. Including each individual's mean sequence read depth across the variant sites in the logistic regression model nearly eliminated the confounding effect and the inflated false-positive rate. Furthermore, accounting for the potential error by modeling the probability of the heterozygote genotype calls in the regression analysis had a relatively minor but beneficial effect on the statistical results. PMID:21328616

  19. Effective modification of particle surface properties using ultrasonic water mist.

    PubMed

    Genina, Natalja; Räikkönen, Heikki; Heinämäki, Jyrki; Antikainen, Osmo; Siiriä, Simo; Veski, Peep; Yliruusi, Jouko

    2009-01-01

    The goal of the present study was to design a new technique to modify particle surface properties and, through that, to improve flowability of poorly flowing drug thiamine hydrochloride and pharmaceutical sugar lactose monohydrate of two different grades. The powdered particles were supplied by a vibratory feeder and exposed to an instantaneous effect of water mist generated from an ultrasound nebulizer. The processed and original powders were evaluated with respect to morphology (scanning electron microscopy, atomic force microscopy, and spatial filtering technique), flow, and solid state properties. It was found that rapid exposition of pharmaceutical materials by water mist resulted in the improvement of powder technical properties. The evident changes in flowability of coarser lactose were obviously due to smoothing of particle surface and decreasing in the level of fines with very slight increment in particle size. The changes in thiamine powder flow were mainly due to narrowing in particle size distribution where the tendency for better flow of finer lactose was related to surface and size modifications. The aqueous mist application did not cause any alteration of the crystal structures of the studied materials. The proposed water mist treatment technique appears to be a robust, rapid, and promising tool for the improvement of the technological properties of pharmaceutical powders. PMID:19288203

  20. Breast milk and cognitive development—the role of confounders: a systematic review

    PubMed Central

    Walfisch, Asnat; Sermer, Corey; Cressman, Alex; Koren, Gideon

    2013-01-01

    Objectives The association between breastfeeding and child cognitive development is conflicted by studies reporting positive and null effects. This relationship may be confounded by factors associated with breastfeeding, specifically maternal socioeconomic class and IQ. Design Systematic review of the literature. Setting and participants Any prospective or retrospective study, in any language, evaluating the association between breastfeeding and cognitive development using a validated method in healthy term infants, children or adults, was included. Primary and secondary outcome measures Extracted data included the study design, target population and sample size, breastfeeding exposure, cognitive development assessment tool used and participants’ age, summary of the results prior to, and following, adjustment for confounders, and all confounders adjusted for. Study quality was assessed as well. Results 84 studies met our inclusion criteria (34 rated as high quality, 26 moderate and 24 low quality). Critical assessment of accepted studies revealed the following associations: 21 null, 28 positive, 18 null after adjusting for confounders and 17 positive—diminished after adjusting for confounders. Directionality of effect did not correlate with study quality; however, studies showing a decreased effect after multivariate analysis were of superior quality compared with other study groupings (14/17 high quality, 82%). Further, studies that showed null or diminished effect after multivariate analysis corrected for significantly more confounders (7.7±3.4) as compared with those that found no change following adjustment (5.6±4.5, p=0.04). The majority of included studies were carried out during childhood (75%) and set in high-income countries (85.5%). Conclusions Much of the reported effect of breastfeeding on child neurodevelopment is due to confounding. It is unlikely that additional work will change the current synthesis. Future studies should attempt to rigorously

  1. Carotta: Revealing Hidden Confounder Markers in Metabolic Breath Profiles

    PubMed Central

    Hauschild, Anne-Christin; Frisch, Tobias; Baumbach, Jörg Ingo; Baumbach, Jan

    2015-01-01

    Computational breath analysis is a growing research area aiming at identifying volatile organic compounds (VOCs) in human breath to assist medical diagnostics of the next generation. While inexpensive and non-invasive bioanalytical technologies for metabolite detection in exhaled air and bacterial/fungal vapor exist and the first studies on the power of supervised machine learning methods for profiling of the resulting data were conducted, we lack methods to extract hidden data features emerging from confounding factors. Here, we present Carotta, a new cluster analysis framework dedicated to uncovering such hidden substructures by sophisticated unsupervised statistical learning methods. We study the power of transitivity clustering and hierarchical clustering to identify groups of VOCs with similar expression behavior over most patient breath samples and/or groups of patients with a similar VOC intensity pattern. This enables the discovery of dependencies between metabolites. On the one hand, this allows us to eliminate the effect of potential confounding factors hindering disease classification, such as smoking. On the other hand, we may also identify VOCs associated with disease subtypes or concomitant diseases. Carotta is an open source software with an intuitive graphical user interface promoting data handling, analysis and visualization. The back-end is designed to be modular, allowing for easy extensions with plugins in the future, such as new clustering methods and statistics. It does not require much prior knowledge or technical skills to operate. We demonstrate its power and applicability by means of one artificial dataset. We also apply Carotta exemplarily to a real-world example dataset on chronic obstructive pulmonary disease (COPD). While the artificial data are utilized as a proof of concept, we will demonstrate how Carotta finds candidate markers in our real dataset associated with confounders rather than the primary disease (COPD) and bronchial

  2. Carotta: Revealing Hidden Confounder Markers in Metabolic Breath Profiles.

    PubMed

    Hauschild, Anne-Christin; Frisch, Tobias; Baumbach, Jörg Ingo; Baumbach, Jan

    2015-01-01

    Computational breath analysis is a growing research area aiming at identifying volatile organic compounds (VOCs) in human breath to assist medical diagnostics of the next generation. While inexpensive and non-invasive bioanalytical technologies for metabolite detection in exhaled air and bacterial/fungal vapor exist and the first studies on the power of supervised machine learning methods for profiling of the resulting data were conducted, we lack methods to extract hidden data features emerging from confounding factors. Here, we present Carotta, a new cluster analysis framework dedicated to uncovering such hidden substructures by sophisticated unsupervised statistical learning methods. We study the power of transitivity clustering and hierarchical clustering to identify groups of VOCs with similar expression behavior over most patient breath samples and/or groups of patients with a similar VOC intensity pattern. This enables the discovery of dependencies between metabolites. On the one hand, this allows us to eliminate the effect of potential confounding factors hindering disease classification, such as smoking. On the other hand, we may also identify VOCs associated with disease subtypes or concomitant diseases. Carotta is an open source software with an intuitive graphical user interface promoting data handling, analysis and visualization. The back-end is designed to be modular, allowing for easy extensions with plugins in the future, such as new clustering methods and statistics. It does not require much prior knowledge or technical skills to operate. We demonstrate its power and applicability by means of one artificial dataset. We also apply Carotta exemplarily to a real-world example dataset on chronic obstructive pulmonary disease (COPD). While the artificial data are utilized as a proof of concept, we will demonstrate how Carotta finds candidate markers in our real dataset associated with confounders rather than the primary disease (COPD) and bronchial

  3. Parenting Practices at 24 to 47 Months and IQ at Age 8: Effect-Measure Modification by Infant Temperament

    PubMed Central

    Chong, Shiau Yun; Chittleborough, Catherine R.; Gregory, Tess; Mittinty, Murthy N.; Lynch, John W.; Smithers, Lisa G.

    2016-01-01

    Cognitive development might be influenced by parenting practices and child temperament. We examined whether the associations between parental warmth, control and intelligence quotient (IQ) may be heightened among children in difficult temperament. Participants were from the Avon Longitudinal Study of Parents and Children (n = 7,044). Temperament at 6 months was measured using the Revised Infant Temperament Questionnaire and classified into ‘easy’ and ‘difficult’. Parental warmth and control was measured at 24 to 47 months and both were classified into 2 groups using latent class analyses. IQ was measured at 8 years using the Wechsler Intelligence Scale for Children and dichotomized (<85 and ≥85) for analyzing effect-measure modification by temperament. Linear regression adjusted for multiple confounders and temperament showed lower parental warmth was weakly associated with lower IQ score [β = -0.52 (95% CI 1.26, 0.21)], and higher parental control was associated with lower IQ score [β = -2.21 (-2.95, -1.48)]. Stratification by temperament showed no increased risk of having low IQ in temperamentally difficult children [risk ratio (RR) = 0.97 95% CI 0.65, 1.45)] but an increased risk among temperamentally easy children (RR = 1.12 95% CI 0.95, 1.32) when parental warmth was low. There was also no increased risk of having low IQ in temperamentally difficult children (RR = 1.02 95% CI 0.69, 1.53) but there was an increased risk among temperamentally easy children (RR = 1.30 95% CI 1.11, 1.53) when parental control was high. For both parental warmth and control, there was some evidence of negative effect-measure modification by temperament on the risk-difference scale and the risk-ratio scale. It may be more appropriate to provide parenting interventions as a universal program rather than targeting children with difficult temperament. PMID:27027637

  4. Parenting Practices at 24 to 47 Months and IQ at Age 8: Effect-Measure Modification by Infant Temperament.

    PubMed

    Chong, Shiau Yun; Chittleborough, Catherine R; Gregory, Tess; Mittinty, Murthy N; Lynch, John W; Smithers, Lisa G

    2016-01-01

    Cognitive development might be influenced by parenting practices and child temperament. We examined whether the associations between parental warmth, control and intelligence quotient (IQ) may be heightened among children in difficult temperament. Participants were from the Avon Longitudinal Study of Parents and Children (n = 7,044). Temperament at 6 months was measured using the Revised Infant Temperament Questionnaire and classified into 'easy' and 'difficult'. Parental warmth and control was measured at 24 to 47 months and both were classified into 2 groups using latent class analyses. IQ was measured at 8 years using the Wechsler Intelligence Scale for Children and dichotomized (<85 and ≥85) for analyzing effect-measure modification by temperament. Linear regression adjusted for multiple confounders and temperament showed lower parental warmth was weakly associated with lower IQ score [β = -0.52 (95% CI 1.26, 0.21)], and higher parental control was associated with lower IQ score [β = -2.21 (-2.95, -1.48)]. Stratification by temperament showed no increased risk of having low IQ in temperamentally difficult children [risk ratio (RR) = 0.97 95% CI 0.65, 1.45)] but an increased risk among temperamentally easy children (RR = 1.12 95% CI 0.95, 1.32) when parental warmth was low. There was also no increased risk of having low IQ in temperamentally difficult children (RR = 1.02 95% CI 0.69, 1.53) but there was an increased risk among temperamentally easy children (RR = 1.30 95% CI 1.11, 1.53) when parental control was high. For both parental warmth and control, there was some evidence of negative effect-measure modification by temperament on the risk-difference scale and the risk-ratio scale. It may be more appropriate to provide parenting interventions as a universal program rather than targeting children with difficult temperament. PMID:27027637

  5. Unique carbon nanotube architectures via surface modification and capillary effects

    NASA Astrophysics Data System (ADS)

    Chakrapani, Nirupama

    dimensions. Pattern formation could also be tailored by prefabricating nanotube arrays by simple lithographic techniques. This study is on the fundamental understanding of capillary effects in dense arrays of ordered nanotubes and the effect of surface modification of nanotubes. This simple self-assembly process is a novel way of creating different macroscopic morphologies and architectures with nanotubes.

  6. The Training Effects of a Behavior Modification Game.

    ERIC Educational Resources Information Center

    Kidder, Steven J.; Guthrie, John T.

    A game designed to teach some of the skills used in behavior modification with slow learners was evaluated. The game, called "Modifying," was developed to increase the range of experience for students preparing to be special education teachers. A randomized, posttest-only design was employed. The design incorporated three treatments: conventional…

  7. Confounding Factors in the Transcriptome Analysis of an In-Vivo Exposure Experiment

    PubMed Central

    Wackers, Paul F. K.; van Oostrom, Conny; Jonker, Martijs J.; Dekker, Rob J.; Rauwerda, Han; Ensink, Wim A.; de Vries, Annemieke; Breit, Timo M.

    2016-01-01

    Confounding factors In transcriptomics experimentation, confounding factors frequently exist alongside the intended experimental factors and can severely influence the outcome of a transcriptome analysis. Confounding factors are regularly discussed in methodological literature, but their actual, practical impact on the outcome and interpretation of transcriptomics experiments is, to our knowledge, not documented. For instance, in-vivo experimental factors; like Individual, Sample-Composition and Time-of-Day are potentially formidable confounding factors. To study these confounding factors, we designed an extensive in-vivo transcriptome experiment (n = 264) with UVR exposure of murine skin containing six consecutive samples from each individual mouse (n = 64). Analysis Approach Evaluation of the confounding factors: Sample-Composition, Time-of-Day, Handling-Stress, and Individual-Mouse resulted in the identification of many genes that were affected by them. These genes sometimes showed over 30-fold expression differences. The most prominent confounding factor was Sample-Composition caused by mouse-dependent skin composition differences, sampling variation and/or influx/efflux of mobile cells. Although we can only evaluate these effects for known cell type specifically expressed genes in our complex heterogeneous samples, it is clear that the observed variations also affect the cumulative expression levels of many other non-cell-type-specific genes. ANOVA ANOVA analysis can only attempt to neutralize the effects of the well-defined confounding factors, such as Individual-Mouse, on the experimental factors UV-Dose and Recovery-Time. Also, by definition, ANOVA only yields reproducible gene-expression differences, but we found that these differences were very small compared to the fold changes induced by the confounding factors, questioning the biological relevance of these ANOVA-detected differences. Furthermore, it turned out that many of the differentially expressed

  8. [Unintended effects of genetic modifications in plants and methods of their analysis].

    PubMed

    Sorochyns'kyĭ, B V; Burlaka, O M; Naumenko, V D; Sekan, A S

    2011-01-01

    The problem of unintended effects caused by genetic modification of plants is analysed. Factors that can provoke the unintended effects in genetically engineered plants, their consequences and possibility of the avoiding of unintended effects with use of current methods of genetic modification are discussed. Modern methodological approaches applied to analyse the unintended effects during the safety assessment of transgenic plants, in particular methods of molecular profiling with different "-omic"-technologies are described. PMID:22168051

  9. Effects of Learner Ability and Instructional Modifications on Time Needed for Learning and Retention.

    ERIC Educational Resources Information Center

    Gettinger, Maribeth

    1983-01-01

    A study examined the effects of two factors--learner ability and modifications of instruction through increased feedback and reduced size of instructional units--on the time required for learning and the retention of fourth-grade male students. While instructional modifications best predicted the time needed for learning, learner ability best…

  10. Burner modifications for cost effective NO{sub x} control

    SciTech Connect

    Melick, T.A.; Payne, R.; Kersch, J.

    1999-11-01

    Low NO{sub x} Burners achieve their NO{sub x} reduction principally by control of the rate of fuel/air mixing. Based on many years of low NO{sub x} burner development experience for wall fired applications, Energy and Environmental Research Corporation (EER) has found that low NO{sub x} fuel/air mixing conditions can be incorporated into conventional burners by modifying the burners as an alternative to complete burner replacement. The NO{sub x} control achieved with such Low NO{sub x} Burner Modifications is, in many cases, comparable to that of new burners but the cost to the utility is much lower. This paper presents an update on EER`s experience in applying Low NO{sub x} Burner Modifications to circular burners focusing on Delmarva Power and Light`s (Connectiv) Indian River Station.

  11. phMRI: methodological considerations for mitigating potential confounding factors

    PubMed Central

    Bourke, Julius H.; Wall, Matthew B.

    2015-01-01

    Pharmacological Magnetic Resonance Imaging (phMRI) is a variant of conventional MRI that adds pharmacological manipulations in order to study the effects of drugs, or uses pharmacological probes to investigate basic or applied (e.g., clinical) neuroscience questions. Issues that may confound the interpretation of results from various types of phMRI studies are briefly discussed, and a set of methodological strategies that can mitigate these problems are described. These include strategies that can be employed at every stage of investigation, from study design to interpretation of resulting data, and additional techniques suited for use with clinical populations are also featured. Pharmacological MRI is a challenging area of research that has both significant advantages and formidable difficulties, however with due consideration and use of these strategies many of the key obstacles can be overcome. PMID:25999812

  12. Review: modifications of human serum albumin and their binding effect.

    PubMed

    Lee, Philbert; Wu, Xiaoyang

    2015-01-01

    Human serum albumin (HSA) regulates the transport and availability of numerous chemical compounds and molecules in the blood vascular system. While previous HSA research has found that HSA interacts with specific varieties of ligands, new research efforts aim to expand HSA's ability to interact with more different drugs in order to improve the delivery of various pharmacological drugs. This review will cover fatty acid chain and posttranslational modifications of HSA that potentially modulate how HSA interacts with various pharmacological drugs, including glycation, cysteinylation, S-nitrosylation, S-transnitrosation and S-guanylation. PMID:25732553

  13. Review: Modifications of Human Serum Albumin and Their Binding Effect

    PubMed Central

    Lee, Philbert; Wu, Xiaoyang

    2015-01-01

    Human serum albumin (HSA) regulates the transport and availability of numerous chemical compounds and molecules in the blood vascular system. While previous HSA research has found that HSA interacts with specific varieties of ligands, new research efforts aim to expand HSA’s ability to interact with more different drugs in order to improve the delivery of various pharmacological drugs. This review will cover fatty acid chain and post-translational modifications of HSA that potentially modulate how HSA interacts with various pharmacological drugs, including glycation, cysteinylation, S-nitrosylation, S-transnitrosation and S-guanylation. PMID:25732553

  14. Adjusting for confounding by neighborhood using complex survey data.

    PubMed

    Brumback, Babette A; He, Zhulin

    2011-04-30

    Recently, we examined methods of adjusting for confounding by neighborhood of an individual exposure effect on a binary outcome, using complex survey data; the methods were found to fail when the neighborhood sample sizes are small and the selection bias is strongly informative. More recently, other authors have adapted an older method from the genetics literature for application to complex survey data; their adaptation achieves a consistent estimator under a broad range of circumstances. The method is based on weighted pseudolikelihoods, in which the contribution from each neighborhood involves all pairs of cases and controls in the neighborhood. The pairs are treated as if they were independent, a pairwise pseudo-conditional likelihood is thus derived, and then the corresponding score equation is weighted with inverse-probabilities of sampling each case-control pair. We have greatly simplified the implementation by translating the pairwise pseudo-conditional likelihood into an equivalent ordinary weighted log-likelihood formulation. We show how to program the method using standard software for ordinary logistic regression with complex survey data (e.g. SAS PROC SURVEYLOGISTIC). We also show that the methodology applies to a broader set of sampling scenarios than the ones considered by the previous authors. We demonstrate the validity of our simplified implementation by applying it to a simulation for which previous methods failed; the new method performs beautifully. We also apply the new method to an analysis of 2009 National Health Interview Survey (NHIS) public-use data, to estimate the effect of education on health insurance coverage, adjusting for confounding by neighborhood. PMID:21287588

  15. Negative Confounding by Essential Fatty Acids in Methylmercury Neurotoxicity Associations

    PubMed Central

    Choi, Anna L; Mogensen, Ulla B.; Bjerve, Kristian S.; Debes, Frodi; Weihe, Pal; Grandjean, Philippe; Budtz-Jørgensen, Esben

    2014-01-01

    Background Methylmercury, a worldwide contaminant of fish and seafood, can cause adverse effects on the developing nervous system. However, long-chain n-3 polyunsaturated fatty acids in seafood provide beneficial effects on brain development. Negative confounding will likely result in underestimation of both mercury toxicity and nutrient benefits unless mutual adjustment is included in the analysis. Methods We examined these associations in 176 Faroese children, in whom prenatal methylmercury exposure was assessed from mercury concentrations in cord blood and maternal hair. The relative concentrations of fatty acids were determined in cord serum phospholipids. Neuropsychological performance in verbal, motor, attention, spatial, and memory functions was assessed at 7 years of age. Multiple regression and structural equation models (SEMs) were carried out to determine the confounder-adjusted associations with methylmercury exposure. Results A short delay recall (in percent change) in the California Verbal Learning Test (CVLT) was associated with a doubling of cord blood methylmercury (−18.9, 95% confidence interval [CI] = −36.3, −1.51). The association became stronger after the inclusion of fatty acid concentrations in the analysis (−22.0, 95% confidence interval [CI] = −39.4, −4.62). In structural equation models, poorer memory function (corresponding to a lower score in the learning trials and short delay recall in CVLT) was associated with a doubling of prenatal exposure to methylmercury after the inclusion of fatty acid concentrations in the analysis (−1.94, 95% CI = −3.39, −0.49). Conclusions Associations between prenatal exposure to methylmercury and neurobehavioral deficits in memory function at school age were strengthened after fatty acid adjustment, thus suggesting that n-3 fatty acids need to be included in analysis of similar studies to avoid underestimation of the associations with methylmercury exposure. PMID:24561639

  16. 75 FR 11559 - Certain Combed Cotton Yarns: Effect of Modification of U.S.-Bahrain FTA Rules of Origin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-11

    ... COMMISSION Certain Combed Cotton Yarns: Effect of Modification of U.S.- Bahrain FTA Rules of Origin AGENCY...-103-025, Certain Combed Cotton Yarns: Effect of Modification of U.S.-Bahrain FTA Rules Of Origin... effect of the proposed modifications on U.S. trade under the U.S.-Bahrain FTA, total U.S. trade, and...

  17. Using instrumental variables to estimate a Cox's proportional hazards regression subject to additive confounding

    PubMed Central

    Tosteson, Tor D.; Morden, Nancy E.; Stukel, Therese A.; O'Malley, A. James

    2014-01-01

    The estimation of treatment effects is one of the primary goals of statistics in medicine. Estimation based on observational studies is subject to confounding. Statistical methods for controlling bias due to confounding include regression adjustment, propensity scores and inverse probability weighted estimators. These methods require that all confounders are recorded in the data. The method of instrumental variables (IVs) can eliminate bias in observational studies even in the absence of information on confounders. We propose a method for integrating IVs within the framework of Cox's proportional hazards model and demonstrate the conditions under which it recovers the causal effect of treatment. The methodology is based on the approximate orthogonality of an instrument with unobserved confounders among those at risk. We derive an estimator as the solution to an estimating equation that resembles the score equation of the partial likelihood in much the same way as the traditional IV estimator resembles the normal equations. To justify this IV estimator for a Cox model we perform simulations to evaluate its operating characteristics. Finally, we apply the estimator to an observational study of the effect of coronary catheterization on survival. PMID:25506259

  18. Sharp sensitivity bounds for mediation under unmeasured mediator-outcome confounding

    PubMed Central

    Ding, Peng; Vanderweele, Tyler J.

    2016-01-01

    It is often of interest to decompose the total effect of an exposure into a component that acts on the outcome through some mediator and a component that acts independently through other pathways. Said another way, we are interested in the direct and indirect effects of the exposure on the outcome. Even if the exposure is randomly assigned, it is often infeasible to randomize the mediator, leaving the mediator-outcome confounding not fully controlled. We develop a sensitivity analysis technique that can bound the direct and indirect effects without parametric assumptions about the unmeasured mediator-outcome confounding.

  19. Restricted spatial regression in practice: Geostatistical models, confounding, and robustness under model misspecification

    USGS Publications Warehouse

    Hanks, Ephraim M.; Schliep, Erin M.; Hooten, Mevin B.; Hoeting, Jennifer A.

    2015-01-01

    In spatial generalized linear mixed models (SGLMMs), covariates that are spatially smooth are often collinear with spatially smooth random effects. This phenomenon is known as spatial confounding and has been studied primarily in the case where the spatial support of the process being studied is discrete (e.g., areal spatial data). In this case, the most common approach suggested is restricted spatial regression (RSR) in which the spatial random effects are constrained to be orthogonal to the fixed effects. We consider spatial confounding and RSR in the geostatistical (continuous spatial support) setting. We show that RSR provides computational benefits relative to the confounded SGLMM, but that Bayesian credible intervals under RSR can be inappropriately narrow under model misspecification. We propose a posterior predictive approach to alleviating this potential problem and discuss the appropriateness of RSR in a variety of situations. We illustrate RSR and SGLMM approaches through simulation studies and an analysis of malaria frequencies in The Gambia, Africa.

  20. Effects of wing modification on an aircraft's aerodynamic parameters as determined from flight data

    NASA Technical Reports Server (NTRS)

    Hess, R. A.

    1986-01-01

    A study of the effects of four wing-leading-edge modifications on a general aviation aircraft's stability and control parameters is presented. Flight data from the basic aircraft configuration and configurations with wing modifications are analyzed to determine each wing geometry's stability and control parameters. The parameter estimates and aerodynamic model forms are obtained using the stepwise regression and maximum likelihood techniques. The resulting parameter estimates and aerodynamic models are verified using vortex-lattice theory and by analysis of each model's ability to predict aircraft behavior. Comparisons of the stability and control derivative estimates from the basic wing and the four leading-edge modifications are accomplished so that the effects of each modification on aircraft stability and control derivatives can be determined.

  1. The Effect of Titanium Surface Modifications on Dental Implant Osseointegration.

    PubMed

    Annunziata, Marco; Guida, Luigi

    2015-01-01

    The use of titanium dental implants has consistently changed the way of rehabilitating patients in modern dentistry and can count on high long-term survival and success rates. With respect to its introduction in the late 1960s, clinical indications for implant therapy have been significantly extended and optimal results have been achieved, even in clinical conditions formerly considered as unfavourable. Such evolution owes a lot to the significant progress made in the field of titanium surfaces. The topographical and chemical modification of traditional titanium surfaces has led to a real epochal shift in implant dentistry. Depending on the type and characteristics of the surface treatment applied, a wide range of implants has been produced, which have contributed to the success but also increased the risk of confusion in implant selection criteria for the clinician. This chapter, which provides an updated analysis of the relevant literature, the characteristics of modern implant surfaces, the biological principles underlying their role in promoting osseointegration and the scientific evidence about their clinical use are analyzed and presented. PMID:26201277

  2. 19 CFR 181.100 - Effect of NAFTA advance ruling letters; modification and revocation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Effect of NAFTA advance ruling letters... Advance Ruling Procedures § 181.100 Effect of NAFTA advance ruling letters; modification and revocation. (a) Effect of NAFTA advance ruling letters—(1) General. An advance ruling letter issued by...

  3. Smoking and Hormesis as Confounding Factors in Radiation Pulmonary Carcinogenesis

    PubMed Central

    Sanders, Charles L.; Scott, Bobby R.

    2008-01-01

    Confounding factors in radiation pulmonary carcinogenesis are passive and active cigarette smoke exposures and radiation hormesis. Significantly increased lung cancer risk from ionizing radiation at lung doses < 1 Gy is not observed in never smokers exposed to ionizing radiations. Residential radon is not a cause of lung cancer in never smokers and may protect against lung cancer in smokers. The risk of lung cancer found in many epi-demiological studies was less than the expected risk (hormetic effect) for nuclear weapons and power plant workers, shipyard workers, fluoroscopy patients, and inhabitants of high-dose background radiation. The protective effect was noted for low- and mixed high- and low-linear energy transfer (LET) radiations in both genders. Many studies showed a protection factor (PROFAC) > 0.40 (40% avoided) against the occurrence of lung cancer. The ubiquitous nature of the radiation hormesis response in cellular, animal, and epidemio-logical studies negates the healthy worker effect as an explanation for radiation hormesis. Low-dose radiation may stimulate DNA repair/apoptosis and immunity to suppress and eliminate cigarette-smoke-induced transformed cells in the lung, reducing lung cancer occurrence in smokers. PMID:18648572

  4. Methods to control for unmeasured confounding in pharmacoepidemiology: an overview.

    PubMed

    Uddin, Md Jamal; Groenwold, Rolf H H; Ali, Mohammed Sanni; de Boer, Anthonius; Roes, Kit C B; Chowdhury, Muhammad A B; Klungel, Olaf H

    2016-06-01

    Background Unmeasured confounding is one of the principal problems in pharmacoepidemiologic studies. Several methods have been proposed to detect or control for unmeasured confounding either at the study design phase or the data analysis phase. Aim of the Review To provide an overview of commonly used methods to detect or control for unmeasured confounding and to provide recommendations for proper application in pharmacoepidemiology. Methods/Results Methods to control for unmeasured confounding in the design phase of a study are case only designs (e.g., case-crossover, case-time control, self-controlled case series) and the prior event rate ratio adjustment method. Methods that can be applied in the data analysis phase include, negative control method, perturbation variable method, instrumental variable methods, sensitivity analysis, and ecological analysis. A separate group of methods are those in which additional information on confounders is collected from a substudy. The latter group includes external adjustment, propensity score calibration, two-stage sampling, and multiple imputation. Conclusion As the performance and application of the methods to handle unmeasured confounding may differ across studies and across databases, we stress the importance of using both statistical evidence and substantial clinical knowledge for interpretation of the study results. PMID:27091131

  5. An education gradient in health, a health gradient in education, or a confounded gradient in both?

    PubMed

    Lynch, Jamie L; von Hippel, Paul T

    2016-04-01

    There is a positive gradient associating educational attainment with health, yet the explanation for this gradient is not clear. Does higher education improve health (causation)? Do the healthy become highly educated (selection)? Or do good health and high educational attainment both result from advantages established early in the life course (confounding)? This study evaluates these competing explanations by tracking changes in educational attainment and Self-rated Health (SRH) from age 15 to age 31 in the National Longitudinal Study of Youth, 1997 cohort. Ordinal logistic regression confirms that high-SRH adolescents are more likely to become highly educated. This is partly because adolescent SRH is associated with early advantages including adolescents' academic performance, college plans, and family background (confounding); however, net of these confounders adolescent SRH still predicts adult educational attainment (selection). Fixed-effects longitudinal regression shows that educational attainment has little causal effect on SRH at age 31. Completion of a high school diploma or associate's degree has no effect on SRH, while completion of a bachelor's or graduate degree have effects that, though significant, are quite small (less than 0.1 points on a 5-point scale). While it is possible that educational attainment would have greater effect on health at older ages, at age 31 what we see is a health gradient in education, shaped primarily by selection and confounding rather than by a causal effect of education on health. PMID:26943010

  6. Effects of Instruction on Adolescent Beginners' Acquisition of Request Modification

    ERIC Educational Resources Information Center

    Li, Qingping

    2012-01-01

    This quasiexperimental study examined the effects of different focus-on-form techniques, and the durability of such effects, on adolescent beginners' acquisition of request supportive moves. Three treatments were implemented: (1) the incidental group was exposed to input and involved in meaningful output activities; (2) the implicit group was…

  7. Counterfactual graphical models for longitudinal mediation analysis with unobserved confounding.

    PubMed

    Shpitser, Ilya

    2013-08-01

    Questions concerning mediated causal effects are of great interest in psychology, cognitive science, medicine, social science, public health, and many other disciplines. For instance, about 60% of recent papers published in leading journals in social psychology contain at least one mediation test (Rucker, Preacher, Tormala, & Petty, 2011). Standard parametric approaches to mediation analysis employ regression models, and either the "difference method" (Judd & Kenny, 1981), more common in epidemiology, or the "product method" (Baron & Kenny, 1986), more common in the social sciences. In this article, we first discuss a known, but perhaps often unappreciated, fact that these parametric approaches are a special case of a general counterfactual framework for reasoning about causality first described by Neyman (1923) and Rubin (1924) and linked to causal graphical models by Robins (1986) and Pearl (2006). We then show a number of advantages of this framework. First, it makes the strong assumptions underlying mediation analysis explicit. Second, it avoids a number of problems present in the product and difference methods, such as biased estimates of effects in certain cases. Finally, we show the generality of this framework by proving a novel result which allows mediation analysis to be applied to longitudinal settings with unobserved confounders. PMID:23899340

  8. Effects of cytosine modifications on DNA flexibility and nucleosome mechanical stability

    NASA Astrophysics Data System (ADS)

    Ngo, Thuy T. M.; Yoo, Jejoong; Dai, Qing; Zhang, Qiucen; He, Chuan; Aksimentiev, Aleksei; Ha, Taekjip

    2016-02-01

    Cytosine can undergo modifications, forming 5-methylcytosine (5-mC) and its oxidized products 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). Despite their importance as epigenetic markers and as central players in cellular processes, it is not well understood how these modifications influence physical properties of DNA and chromatin. Here we report a comprehensive survey of the effect of cytosine modifications on DNA flexibility. We find that even a single copy of 5-fC increases DNA flexibility markedly. 5-mC reduces and 5-hmC enhances flexibility, and 5-caC does not have a measurable effect. Molecular dynamics simulations show that these modifications promote or dampen structural fluctuations, likely through competing effects of base polarity and steric hindrance, without changing the average structure. The increase in DNA flexibility increases the mechanical stability of the nucleosome and vice versa, suggesting a gene regulation mechanism where cytosine modifications change the accessibility of nucleosomal DNA through their effects on DNA flexibility.

  9. Effects of cytosine modifications on DNA flexibility and nucleosome mechanical stability

    PubMed Central

    Ngo, Thuy T. M.; Yoo, Jejoong; Dai, Qing; Zhang, Qiucen; He, Chuan; Aksimentiev, Aleksei; Ha, Taekjip

    2016-01-01

    Cytosine can undergo modifications, forming 5-methylcytosine (5-mC) and its oxidized products 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). Despite their importance as epigenetic markers and as central players in cellular processes, it is not well understood how these modifications influence physical properties of DNA and chromatin. Here we report a comprehensive survey of the effect of cytosine modifications on DNA flexibility. We find that even a single copy of 5-fC increases DNA flexibility markedly. 5-mC reduces and 5-hmC enhances flexibility, and 5-caC does not have a measurable effect. Molecular dynamics simulations show that these modifications promote or dampen structural fluctuations, likely through competing effects of base polarity and steric hindrance, without changing the average structure. The increase in DNA flexibility increases the mechanical stability of the nucleosome and vice versa, suggesting a gene regulation mechanism where cytosine modifications change the accessibility of nucleosomal DNA through their effects on DNA flexibility. PMID:26905257

  10. Surface Modifications and Their Effects on Titanium Dental Implants

    PubMed Central

    Jemat, A.; Ghazali, M. J.; Razali, M.; Otsuka, Y.

    2015-01-01

    This review covers several basic methodologies of surface treatment and their effects on titanium (Ti) implants. The importance of each treatment and its effects will be discussed in detail in order to compare their effectiveness in promoting osseointegration. Published literature for the last 18 years was selected with the use of keywords like titanium dental implant, surface roughness, coating, and osseointegration. Significant surface roughness played an important role in providing effective surface for bone implant contact, cell proliferation, and removal torque, despite having good mechanical properties. Overall, published studies indicated that an acid etched surface-modified and a coating application on commercial pure titanium implant was most preferable in producing the good surface roughness. Thus, a combination of a good surface roughness and mechanical properties of titanium could lead to successful dental implants. PMID:26436097

  11. Effects of different substrate surface modifications on the epitaxial ZnO/Si

    NASA Astrophysics Data System (ADS)

    Wang, Peng; Jin, Changlian; Zhan, Huahan; Chen, Xiaohang; Xu, Fuchun; Zhou, Yinghui; Wang, Huiqiong; Kang, Junyong

    2013-09-01

    To produce high quality ZnO/Si for the applications in short wavelength optoelectronic devices, the effects of different silicon surface modifications on the overgrown ZnO thin film were investigated. Samples were grown by a plasma assistant molecular beam epitaxy at room temperature, avoiding the oxidation of the Si surface and the thermal stress caused by difference of the thermal expansion coefficients between ZnO and silicon. Different modifications on the Si(100) substrate surface including nitridation, oxidation, and depositions of Mg and Zn, were employed. The effects on the overgrown ZnO layers and the interlayer SiOx were investigated by atomic force microscopy, photoluminescence, X-ray diffraction and auger depth electron spectroscopy. All the modifications were effective in different degrees at reducing the SiOx amorphous layer. However, different mechanisms resulted in distinct performance in crystal structure and optical property.

  12. The effects of beta-endorphin: state change modification.

    PubMed

    Veening, Jan G; Barendregt, Henk P

    2015-01-01

    Beta-endorphin (β-END) is an opioid neuropeptide which has an important role in the development of hypotheses concerning the non-synaptic or paracrine communication of brain messages. This kind of communication between neurons has been designated volume transmission (VT) to differentiate it clearly from synaptic communication. VT occurs over short as well as long distances via the extracellular space in the brain, as well as via the cerebrospinal fluid (CSF) flowing through the ventricular spaces inside the brain and the arachnoid space surrounding the central nervous system (CNS). To understand how β-END can have specific behavioral effects, we use the notion behavioral state, inspired by the concept of machine state, coming from Turing (Proc London Math Soc, Series 2,42:230-265, 1937). In section 1.4 the sequential organization of male rat behavior is explained showing that an animal is not free to switch into another state at any given moment. Funneling-constraints restrict the number of possible behavioral transitions in specific phases while at other moments in the sequence the transition to other behavioral states is almost completely open. The effects of β-END on behaviors like food intake and sexual behavior, and the mechanisms involved in reward, meditation and pain control are discussed in detail. The effects on the sequential organization of behavior and on state transitions dominate the description of these effects. PMID:25879522

  13. Adjusting for unmeasured confounding due to either of two crossed factors with a logistic regression model.

    PubMed

    Li, Li; Brumback, Babette A; Weppelmann, Thomas A; Morris, J Glenn; Ali, Afsar

    2016-08-15

    Motivated by an investigation of the effect of surface water temperature on the presence of Vibrio cholerae in water samples collected from different fixed surface water monitoring sites in Haiti in different months, we investigated methods to adjust for unmeasured confounding due to either of the two crossed factors site and month. In the process, we extended previous methods that adjust for unmeasured confounding due to one nesting factor (such as site, which nests the water samples from different months) to the case of two crossed factors. First, we developed a conditional pseudolikelihood estimator that eliminates fixed effects for the levels of each of the crossed factors from the estimating equation. Using the theory of U-Statistics for independent but non-identically distributed vectors, we show that our estimator is consistent and asymptotically normal, but that its variance depends on the nuisance parameters and thus cannot be easily estimated. Consequently, we apply our estimator in conjunction with a permutation test, and we investigate use of the pigeonhole bootstrap and the jackknife for constructing confidence intervals. We also incorporate our estimator into a diagnostic test for a logistic mixed model with crossed random effects and no unmeasured confounding. For comparison, we investigate between-within models extended to two crossed factors. These generalized linear mixed models include covariate means for each level of each factor in order to adjust for the unmeasured confounding. We conduct simulation studies, and we apply the methods to the Haitian data. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26892025

  14. The Effect of Decitabine Dose Modification and Myelosuppression on Response and Survival in Patients With Myelodysplastic Syndromes

    PubMed Central

    Jabbour, Elias; Garcia-Manero, Guillermo; Cornelison, A. Megan; Cortes, Jorge E.; Ravandi, Farhad; Daver, Naval; Kadia, Tapan; Teng, Angela; Kantarjian, Hagop

    2014-01-01

    Myelosuppression in myelodysplastic syndromes (MDS) is associated with the hypomethylating agent decitabine. A retrospective pooled analysis of 2 decitabine clinical trials in patients with MDS conducted Cox regression analyses of red blood cell or platelet dependence, myelosuppression, dose modification, cycle delay or dose reduction, and survival effects. In 182 patients, baseline platelet dependence was a predictor for dose modification, reduction, or delay, and death (modification: P = .006, hazard ratio [HR] = 2.04; reduction/delay: P = .011, HR = 2.00; death: P = .003, HR = 1.94). Patients with dose modifications had significantly higher overall response rates versus those with none (22% vs 10%; P = .015). Patients with no dose modifications had faster progression to AML versus patients with dose modifications (P = .004). Without dose modifications, patients tended to drop out due to disease progression or other reasons. Decitabine dose modifications on treatment may indicate response to treatment. PMID:24844364

  15. Inflammatory effects of Edwardsiella ictaluri lipopolysaccharide modifications in catfish gut.

    PubMed

    Santander, Javier; Kilbourne, Jacquelyn; Park, Jie-Yeun; Martin, Taylor; Loh, Amanda; Diaz, Ignacia; Rojas, Robert; Segovia, Cristopher; DeNardo, Dale; Curtiss, Roy

    2014-08-01

    Bacterial lipopolysaccharides (LPS) are structural components of the outer membranes of Gram-negative bacteria and also are potent inducers of inflammation in mammals. Higher vertebrates are extremely sensitive to LPS, but lower vertebrates, like fish, are resistant to their systemic toxic effects. However, the effects of LPS on the fish intestinal mucosa remain unknown. Edwardsiella ictaluri is a primitive member of the Enterobacteriaceae family that causes enteric septicemia in channel catfish (Ictalurus punctatus). E. ictaluri infects and colonizes deep lymphoid tissues upon oral or immersion infection. Both gut and olfactory organs are the primary sites of invasion. At the systemic level, E. ictaluri pathogenesis is relatively well characterized, but our knowledge about E. ictaluri intestinal interaction is limited. Recently, we observed that E. ictaluri oligo-polysaccharide (O-PS) LPS mutants have differential effects on the intestinal epithelia of orally inoculated catfish. Here we evaluate the effects of E. ictaluri O-PS LPS mutants by using a novel catfish intestinal loop model and compare it to the rabbit ileal loop model inoculated with Salmonella enterica serovar Typhimurium LPS. We found evident differences in rabbit ileal loop and catfish ileal loop responses to E. ictaluri and S. Typhimurium LPS. We determined that catfish respond to E. ictaluri LPS but not to S. Typhimurium LPS. We also determined that E. ictaluri inhibits cytokine production and induces disruption of the intestinal fish epithelia in an O-PS-dependent fashion. The E. ictaluri wild type and ΔwibT LPS mutant caused intestinal tissue damage and inhibited proinflammatory cytokine synthesis, in contrast to E. ictaluri Δgne and Δugd LPS mutants. We concluded that the E. ictaluri O-PS subunits play a major role during pathogenesis, since they influence the recognition of the LPS by the intestinal mucosal immune system of the catfish. The LPS structure of E. ictaluri mutants is needed to

  16. Effects of cementation surface modifications on fracture resistance of zirconia

    PubMed Central

    Srikanth, Ramanathan; Kosmac, Tomaz; Bona, Alvaro Della; Yin, Ling; Zhang, Yu

    2015-01-01

    Objectives To examine the effects of glass infiltration (GI) and alumina coating (AC) on the indentation flexural load and four-point bending strength of monolithic zirconia. Methods Plate-shaped (12 mm × 12 mm × 1.0 mm or 1.5 mm or 2.0 mm) and bar-shaped (4 mm × 3 mm × 25 mm) monolithic zirconia specimens were fabricated. In addition to monolithic zirconia (group Z), zirconia monoliths were glass-infiltrated or alumina-coated on their tensile surfaces to form groups ZGI and ZAC, respectively. They were also glass-infiltrated on their upper surfaces, and glass-infiltrated or alumina-coated on their lower (tensile) surfaces to make groups ZGI2 and ZAC2, respectively. For comparison, porcelain-veneered zirconia (group PVZ) and monolithic lithium disilicate glass-ceramic (group LiDi) specimens were also fabricated. The plate-shaped specimens were cemented onto a restorative composite base for Hertzian indentation using a tungsten carbide spherical indenter with a radius of 3.2 mm. Critical loads for indentation flexural fracture at the zirconia cementation surface were measured. Strengths of bar-shaped specimens were evaluated in four-point bending. Results Glass infiltration on zirconia tensile surfaces increased indentation flexural loads by 32% in Hertzian contact and flexural strength by 24% in four-point bending. Alumina coating showed no significant effect on resistance to flexural damage of zirconia. Monolithic zirconia outperformed porcelain-veneered zirconia and monolithic lithium disilicate glass-ceramics in terms of both indentation flexural load and flexural strength. Significance While both alumina coating and glass infiltration can be used to effectively modify the cementation surface of zirconia, glass infiltration can further increase the flexural fracture resistance of zirconia. PMID:25687628

  17. Effect of Structural Modification on Second Harmonic Generation in Collagen

    SciTech Connect

    Stoller, P C; Reiser, K M; Celliers, P M; Rubenchik, A M

    2003-04-04

    The effects of structural perturbation on second harmonic generation in collagen were investigated. Type I collagen fascicles obtained from rat tails were structurally modified by increasing nonenzymatic cross-linking, by thermal denaturation, by collagenase digestion, or by dehydration. Changes in polarization dependence were observed in the dehydrated samples. Surprisingly, no changes in polarization dependence were observed in highly crosslinked samples, despite significant alterations in packing structure. Complete thermal denaturation and collagenase digestion produced samples with no detectable second harmonic signal. Prior to loss of signal, no change in polarization dependence was observed in partially heated or digested collagen.

  18. The Effects of Approach-Avoidance Modification on Social Anxiety Disorder: A Pilot Study

    PubMed Central

    Asnaani, Anu; Rinck, Mike; Becker, Eni; Hofmann, Stefan G.

    2014-01-01

    Cognitive bias modification has recently been discussed as a possible intervention for mental disorders. A specific form of this novel treatment approach is approach-avoidance modification. In order to examine the efficacy of approach-avoidance modification for positive stimuli associated with social anxiety, we recruited 43 individuals with social anxiety disorder and randomly assigned them to a training (implicit training to approach smiling faces) or a control (equal approach and avoidance of smiling faces) condition in three sessions over the course of a one-week period. Dependent measures included clinician ratings, self-report measures of social anxiety, and overt behavior during behavioral approach tasks. No group differences in any of the outcome measures were observed after training. In addition, while individuals in the training group showed increased approach tendency in one of the sessions, this effect was inconsistent across the three sessions and did not result in long-term changes in implicit approach tendencies between the groups over the course of the entire study. These results suggest that approach-avoidance modification might result in short-lasting effects on implicit approach tendencies towards feared positive stimuli, but this modification may not result in meaningful behavioral change or symptom reduction in individuals with social anxiety disorder. PMID:24659832

  19. Bentonite modification with hexadecylpyridinium and aluminum polyoxy cations and its effectiveness in Se(IV) removal.

    PubMed

    Orucoglu, Esra; Haciyakupoglu, Sevilay

    2015-09-01

    Usage of bentonite as a buffer material is suggested in radioactive waste repositories. Although bentonites have higher sorption ability to cations, they cannot adsorp anions due to negative surface charge. Nowadays, ongoing researches focus on increasing anion adsorption ability of the bentonites with modification. Organic-pillared bentonite (OPBent) was produced by modification of sodium bentonite with aluminum polyoxy and hexadecylpyridinium cations in this study. Variation in structure after modification was demonstrated by using different characterization techniques. Se removal efficiency of OPBent is investigated by using (75)Se, since selenium (Se) is one of the important long lived fission products found in radioactive waste and has toxic anionic species in an aqueous environment. The effect of reaction time, solid/liquid ratio, pH and concentration on the adsorption performance were examined. Se speciation and its effect onto adsorption were also investigated by measuring Eh-pH values under certain experimental conditions. Additionally, importance of the amount of Al-polyoxy cations used in modification was investigated by comparing these results with the results of other organic-pillared bentonite produced in our previous research. Experimental results confirmed that both cations were successfully placed into the bentonite interlayer and significant change in the host structure leads to increase Se adsorption. Consequently, bentonite modification improves its Se adsorption ability and further investigations are needed related to the usage of this adsorbent in other remediation studies especially in sorption of other anionic pollutants. PMID:26081306

  20. Combating Unmeasured Confounding in Cross-Sectional Studies: Evaluating Instrumental-Variable and Heckman Selection Models

    PubMed Central

    DeMaris, Alfred

    2014-01-01

    Unmeasured confounding is the principal threat to unbiased estimation of treatment “effects” (i.e., regression parameters for binary regressors) in nonexperimental research. It refers to unmeasured characteristics of individuals that lead them both to be in a particular “treatment” category and to register higher or lower values than others on a response variable. In this article, I introduce readers to 2 econometric techniques designed to control the problem, with a particular emphasis on the Heckman selection model (HSM). Both techniques can be used with only cross-sectional data. Using a Monte Carlo experiment, I compare the performance of instrumental-variable regression (IVR) and HSM to that of ordinary least squares (OLS) under conditions with treatment and unmeasured confounding both present and absent. I find HSM generally to outperform IVR with respect to mean-square-error of treatment estimates, as well as power for detecting either a treatment effect or unobserved confounding. However, both HSM and IVR require a large sample to be fully effective. The use of HSM and IVR in tandem with OLS to untangle unobserved confounding bias in cross-sectional data is further demonstrated with an empirical application. Using data from the 2006–2010 General Social Survey (National Opinion Research Center, 2014), I examine the association between being married and subjective well-being. PMID:25110904

  1. Dual-effect laser handpiece for modification of tissue permeability

    NASA Astrophysics Data System (ADS)

    McMillan, Kathleen

    2011-03-01

    A new approach for improving the availability of topically applied drugs by reducing the permeability of dermis has been evaluated. The premise of this work is that photothermal vascular injury will reduce vascular uptake of drug in the dermis. The dermal distribution of two topically applied drugs, 5-fluorouracil and mitomycin C, is calculated, considering molecular diffusion and vascular uptake according to a distributed model, in the presence and absence of vascular injury. Intradermal drug exposures obtained are compared to exposures known to be effective in killing tumor cells. Combining the reduction in dermal permeability with fractional photothermal epidermal ablation to increase epidermal permeability may allow higher drug concentrations to be achieved in the skin. A newly developed laser handpiece for implementing the technique is described.

  2. Effect of Surface Modification and Macrophage Phenotype on Particle Internalization

    SciTech Connect

    Wang, Daniel; Phan, Ngoc; Isely, Christopher; Bruene, Lucas; Bratlie, Kaitlin M

    2014-11-10

    Material properties play a key role in the cellular internalization of polymeric particles. In the present study, we have investigated the effects of material characteristics such as water contact angle, zeta potential, melting temperature, and alternative activation of complement on particle internalization for pro-inflammatory, pro-angiogenic, and naïve macrophages by using biopolymers (~600 nm), functionalized with 13 different molecules. Understanding how material parameters influence particle internalization for different macrophage phenotypes is important for targeted delivery to specific cell populations. Here, we demonstrate that material parameters affect the alternative pathway of complement activation as well as particle internalization for different macrophage phenotypes. Here, we show that the quantitative structure–activity relationship method (QSAR) previously used to predict physiochemical properties of materials can be applied to targeting different macrophage phenotypes. These findings demonstrated that targeted drug delivery to macrophages could be achieved by exploiting material parameters.

  3. Scalar Modifications to Gravity from Unparticle Effects May Be Testable

    SciTech Connect

    Goldberg, Haim; Nath, Pran

    2008-01-25

    Interest has focused recently on low energy implications of a nontrivial scale invariant sector of an effective field theory with an IR fixed point, manifest in terms of 'unparticles' with peculiar properties. If unparticle stuff exists it could couple to the stress tensor and mediate a new 'fifth' force ('ungravity'). Under the assumption of strict conformal invariance in the hidden sector down to low energies, we compute the lowest order ungravity correction to the Newtonian gravitational potential and find scale invariant power law corrections of type (R{sub G}/r){sup 2d{sub U}-1}, where d{sub U} is an anomalous unparticle dimension and R{sub G} is a characteristic length scale where the ungravity interactions become significant. It is shown that a discrimination between extra dimension models and ungravity is possible in future improved submillimeter tests of gravity.

  4. Packet Randomized Experiments for Eliminating Classes of Confounders

    PubMed Central

    Pavela, Greg; Wiener, Howard; Fontaine, Kevin R.; Fields, David A.; Voss, Jameson D.; Allison, David B.

    2014-01-01

    Background Although randomization is considered essential for causal inference, it is often not possible to randomize in nutrition and obesity research. To address this, we develop a framework for an experimental design—packet randomized experiments (PREs), which improves causal inferences when randomization on a single treatment variable is not possible. This situation arises when subjects are randomly assigned to a condition (such as a new roommate) which varies in one characteristic of interest (such as weight), but also varies across many others. There has been no general discussion of this experimental design, including its strengths, limitations, and statistical properties. As such, researchers are left to develop and apply PREs on an ad hoc basis, limiting its potential to improve causal inferences among nutrition and obesity researchers. Methods We introduce PREs as an intermediary design between randomized controlled trials and observational studies. We review previous research that used the PRE design and describe its application in obesity-related research, including random roommate assignments, heterochronic parabiosis, and the quasi-random assignment of subjects to geographic areas. We then provide a statistical framework to control for potential packet-level confounders not accounted for by randomization. Results PREs have successfully been used to improve causal estimates of the effect of roommates, altitude, and breastfeeding on weight outcomes. When certain assumptions are met, PREs can asymptotically control for packet-level characteristics. This has the potential to statistically estimate the effect of a single treatment even when randomization to a single treatment did not occur. Conclusions Applying PREs to obesity-related research will improve decisions about clinical, public health, and policy actions insofar as it offers researchers new insight into cause and effect relationships among variables. PMID:25444088

  5. Air Pollution and Autism Spectrum Disorders: Causal or Confounded?

    PubMed

    Weisskopf, Marc G; Kioumourtzoglou, Marianthi-Anna; Roberts, Andrea L

    2015-12-01

    In the last decade, several studies have examined the association between perinatal exposure to ambient air pollution and risk of autism spectrum disorder (ASD). These studies have largely been consistent, with associations seen with different aspects of air pollution, including hazardous air toxics, ozone, particulate, and traffic-related pollution. Confounding by socioeconomic status (SES) and place of residence are of particular concern, as these can be related to ASD case ascertainment and other potential causal risk factors for ASD. While all studies take steps to address this concern, residual confounding is difficult to rule out. Two recent studies of air pollution and ASD, however, present findings that strongly argue against residual confounding, especially for factors that do not vary over relatively short time intervals. These two studies, conducted in communities around the USA, found a specific association with air pollution exposure during the 3rd, but not the 1st, trimester, when both trimesters were modeled simultaneously. In this review, we discuss confounding possibilities and then explain-with the aid of directed acyclic graphs (DAGs)-why an association that is specific to a particular time window, when multiple exposure windows are simultaneously assessed, argues against residual confounding by (even unmeasured) non-time-varying factors. In addition, we discuss why examining ambient air pollution concentration as a proxy for personal exposure helps avoid confounding by personal behavior differences, and the implications of measurement error in using ambient concentrations as a proxy for personal exposures. Given the general consistency of findings across studies and the exposure-window-specific associations recently reported, the overall evidence for a causal association between air pollution and ASD is increasingly compelling. PMID:26399256

  6. Effect of plasma surface modification on the biocompatibility of UHMWPE.

    PubMed

    Kaklamani, G; Mehrban, N; Chen, J; Bowen, J; Dong, H; Grover, L; Stamboulis, A

    2010-10-01

    In this paper active screen plasma nitriding (ASPN) is used to chemically modify the surface of UHMWPE. This is an unexplored and new area of research. ASPN allows the homogeneous treatment of any shape or surface at low temperature; therefore, it was thought that ASPN would be an effective technique to modify organic polymer surfaces. ASPN experiments were carried out at 120 °C using a dc plasma nitriding unit with a 25% N(2) and 75% H(2) atmosphere at 2.5 mbar of pressure. UHMWPE samples treated for different time periods were characterized by nanoindentation, FTIR, XPS, interferometry and SEM. A 3T3 fibroblast cell line was used for in vitro cell culture experiments. Nanoindentation of UHMWPE showed that hardness and elastic modulus increased with ASPN treatment compared to the untreated material. FTIR spectra did not show significant differences between the untreated and treated samples; however, some changes were observed at 30 min of treatment in the range of 1500-1700 cm(-1) associated mainly with the presence of N-H groups. XPS studies showed that nitrogen was present on the surface and its amount increased with treatment time. Interferometry showed that no significant changes were observed on the surfaces after the treatment. Finally, cell culture experiments and SEM showed that fibroblasts attached and proliferated to a greater extent on the plasma-treated surfaces leading to the conclusion that ASPN surface treatment can potentially significantly improve the biocompatibility behaviour of polymeric materials. PMID:20876959

  7. Effects of Lexical Modification on Incidental Vocabulary Acquisition of Iranian EFL Students

    ERIC Educational Resources Information Center

    Negari, Giti Mousapour; Rouhi, Mahdieh

    2012-01-01

    The present article reports on the results of a study designed to investigate the effects of two types of lexical modification i.e., lexical simplification and elaboration, on incidental vocabulary acquisition of Iranian EFL learners.To this end, four versions of experimental texts containing 20 target words were created: baseline and simplified…

  8. Effecting Behavioral Modification in the Mentally Handicapped Student: Operant Conditioning and the Teacher's Role.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Div. for Handicapped Children.

    Presented are nine short papers concerning teacher role in effecting behavioral modification in the mentally handicapped student. The paper on functional analysis of behavior discusses use of reinforcers, changing reinforcer strength, reinforcement schedules, and discriminative stimuli. A continuation paper on functional analysis of behavior…

  9. Effect of the surface topographic modification on cytocompatibility of hardened calcium phosphate cement

    NASA Astrophysics Data System (ADS)

    Li, Jiyan; He, Fupo; Ye, Jiandong

    2013-06-01

    As cells are inherently sensitive to local nanoscale patterns of topography, the aim of this study was to determine the effect of the topographic modification of hardened calcium phosphate cement on cell response which was conducted with MC3T3-E1 cells. The results exhibited that the samples with regular blade-like crystalline structure had better cell response (cell attachment, viability, proliferation and differentiation) compared to those with irregular blade-like crystalline structure. The method of topographic modification is promising for developing a novel biomaterial of hardened calcium phosphate cement for bone repair.

  10. Effect of adipic dihydrazide modification on the performance of collagen/hyaluronic acid scaffold.

    PubMed

    Zhang, Ling; Xiao, Yumei; Jiang, Bo; Fan, Hongsong; Zhang, Xingdong

    2010-02-01

    Collagen and hydrazide-functionalized hyaluronic acid derivatives were hybridized by gelating and genipin crosslinking to form composite hydrogel. The study contributed to the understanding of the effects of adipic dihydrazide modification on the physicochemical and biological properties of the collagen/hyaluronic acid scaffold. The investigation included morphology observation, mechanical measurement, swelling evaluation, and collagenase degradation. The results revealed that the stability of composites was increased through adipic dihydrazide modification and genipin crosslinking. The improved biocompatibility and retention of hyaluronic acid made the composite material more favorable to chondrocytes growing, suggesting the prepared scaffold might be high potential for chondrogenesis. PMID:19810117

  11. The effects of linguistic modification on ESL students' comprehension of nursing course test items.

    PubMed

    Bosher, Susan; Bowles, Melissa

    2008-01-01

    Recent research has indicated that language may be a source of construct-irrelevant variance for non-native speakers of English, or English as a second language (ESL) students, when they take exams. As a result, exams may not accurately measure knowledge of nursing content. One accommodation often used to level the playing field for ESL students is linguistic modification, a process by which the reading load of test items is reduced while the content and integrity of the item are maintained. Research on the effects of linguistic modification has been conducted on examinees in the K-12 population, but is just beginning in other areas. This study describes the collaborative process by which items from a pathophysiology exam were linguistically modified and subsequently evaluated for comprehensibility by ESL students. Findings indicate that in a majority of cases, modification improved examinees' comprehension of test items. Implications for test item writing and future research are discussed. PMID:18575241

  12. Effect of edge modification on the zigzag BC2N nanoribbons

    NASA Astrophysics Data System (ADS)

    Xiao, Xiang; Li, Hong; Tie, Jun; Lu, Jing

    2016-08-01

    We use first principles calculations to investigate the effects of edge modification with nonmetal species on zigzag-edged BC2N nanoribbons (ZBC2NNRs). These ZBC2NNRs show either semiconducting or metallic behaviors depending on the edge modifications and ribbon widths. We find that the O-modification induces a ferromagnetic ground state with a metallic behavior for all the ribbon widths investigated. And when the ribbon width is more than 3.32 nm (NZ ⩾ 16), an antiferromagnetic ground state with a half-metallic behavior is realized in the H-passivated ZBC2NNRs. These versatile electronic properties render the ZBC2NNRs a promising candidate material in nanoelectronics and nanospintronics.

  13. Investigation of the Effect of Oil Modification on Critical Characteristics of Asphalt Binders

    NASA Astrophysics Data System (ADS)

    Golalipour, Amir

    Thermally induced cracking of asphalt pavement continues to be a serious issue in cold climate regions as well as in areas which experience extreme daily temperature differentials. Low temperature cracking of asphalt pavements is attributed to thermal stresses and strains developed during cooling cycles. Improving asphalt binder low temperature fracture and stiffness properties continues to be a subject of particular concern. Therefore, significant amount of research has been focused on improving asphalt binder properties through modification. In recent years, wide ranges of oil based modifications have been introduced to improve asphalt binder performance, especially at the low service temperatures. Although, significant use of these oils is seen in practice, knowledge of the fundamental mechanisms of oil modification and their properties for achieving optimum characteristics is limited. Hence, this study focuses on better understanding of the effect of oil modifiers which would help better material selection and achieve optimum performance in terms of increasing the life span of pavements. In this study, the effect of oil modification on the rheological properties of the asphalt binder is investigated. To examine the effect of oil modification on binder characteristics, low temperature properties as well as high temperature performance of oil modified binders were evaluated. It is found that oils vary in their effects on asphalt binder performance. However, for all oils used in the study, adding an oil to binder can improve binder low temperature performance, and this result mainly attributed to the softening effect. In addition to that, a simple linear model is proposed to predict the performance grade of oil modified binder based on the properties of its constituents at high and low temperatures. Another part of this study focuses on the oil modification effect on asphalt binder thermal strain and stresses. A viscoelastic analytical procedure is combined with

  14. Acute effects of air pollution on pediatric asthma exacerbation: evidence of association and effect modification.

    PubMed

    Samoli, E; Nastos, P T; Paliatsos, A G; Katsouyanni, K; Priftis, K N

    2011-04-01

    We investigated the short-term effects of particulate matter with aerodynamic diameter <10 μg/m(3) (PM(10)), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)) and ozone (O(3)) on pediatric asthma emergency admissions in Athens, Greece over the period 2001-2004. We explored effect modification patterns by season, sex, age and by the presence of desert dust transported mainly from the Sahara area. We used daily time-series data provided by the children's hospitals and the fixed monitoring stations. The associations were investigated using Poisson regression models controlling for seasonality, weather, influenza episodes, day of the week and holiday effects. A 10 μg/m(3) increase in PM(10) was associated with a 2.54% increase (95% confidence interval (CI): 0.06%, 5.08%) in the number of pediatric asthma hospital admissions, while the same increase in SO(2) was associated with a 5.98% (95% CI: 0.88%, 11.33%) increase. O(3) was associated with a statistically significant increase in asthma admissions among older children in the summer. Our findings provide limited evidence of an association between NO(2) exposure and asthma exacerbation. Statistically significant PM(10) effects were higher during winter and during desert dust days, while SO(2) effects occurred mainly during spring. Our study confirms previously reported PM(10) effects on emergency hospital admissions for pediatric asthma and further provides evidence of stronger effects during desert dust days. We additionally report severe effects of SO(2), even at today's low concentration levels. PMID:21296347

  15. The Threshold of Embedded M Collider Bias and Confounding Bias

    ERIC Educational Resources Information Center

    Kelcey, Benjamin; Carlisle, Joanne

    2011-01-01

    Of particular import to this study, is collider bias originating from stratification on retreatment variables forming an embedded M or bowtie structural design. That is, rather than assume an M structural design which suggests that "X" is a collider but not a confounder, the authors adopt what they consider to be a more reasonable position and…

  16. Doubly robust methods for handling confounding by cluster.

    PubMed

    Zetterqvist, Johan; Vansteelandt, Stijn; Pawitan, Yudi; Sjölander, Arvid

    2016-04-01

    In clustered designs such as family studies, the exposure-outcome association is usually confounded by both cluster-constant and cluster-varying confounders. The influence of cluster-constant confounders can be eliminated by studying the exposure-outcome association within (conditional on) clusters, but additional regression modeling is usually required to control for observed cluster-varying confounders. A problem is that the working regression model may be misspecified, in which case the estimated within-cluster association may be biased. To reduce sensitivity to model misspecification we propose to augment the standard working model for the outcome with an auxiliary working model for the exposure. We derive a doubly robust conditional generalized estimating equation (DRCGEE) estimator for the within-cluster association. This estimator combines the two models in such a way that it is consistent if either model is correct, not necessarily both. Thus, the DRCGEE estimator gives the researcher two chances instead of only one to make valid inference on the within-cluster association. We have implemented the estimator in an R package and we use it to examine the association between smoking during pregnancy and cognitive abilities in offspring, in a sample of siblings. PMID:26508769

  17. Effects of Weak Surface Modification on Co/SiO2 Catalyst for Fischer-Tropsch Reaction.

    PubMed

    Ning, Wensheng; Shen, Hehong; Jin, Yangfu; Yang, Xiazhen

    2015-01-01

    A weak surface modification is applied to Co/SiO2 catalyst by hydrothermal treatment at 180°C for 5 h. Aluminum is introduced to Co/SiO2 catalysts during the surface modification. The effects of surface modification on Co/SiO2 catalyst are studied by changing the operating sequences of surface modification and cobalt impregnation in the catalyst preparation. Surface modification before cobalt impregnation makes Co3O4 particle small and dispersed into the deep part of enlarged pore in SiO2, while surface modification after cobalt impregnation does not obviously change the particle size of Co3O4. The improved amplitude of catalytic activity is similar for the two kinds of catalysts, but they are benefited from different factors. The content of iso-hydrocarbons in the products is increased by the surface modifications. PMID:25938725

  18. Effects of Weak Surface Modification on Co/SiO2 Catalyst for Fischer-Tropsch Reaction

    PubMed Central

    Ning, Wensheng; Shen, Hehong; Jin, Yangfu; Yang, Xiazhen

    2015-01-01

    A weak surface modification is applied to Co/SiO2 catalyst by hydrothermal treatment at 180°C for 5 h. Aluminum is introduced to Co/SiO2 catalysts during the surface modification. The effects of surface modification on Co/SiO2 catalyst are studied by changing the operating sequences of surface modification and cobalt impregnation in the catalyst preparation. Surface modification before cobalt impregnation makes Co3O4 particle small and dispersed into the deep part of enlarged pore in SiO2, while surface modification after cobalt impregnation does not obviously change the particle size of Co3O4. The improved amplitude of catalytic activity is similar for the two kinds of catalysts, but they are benefited from different factors. The content of iso-hydrocarbons in the products is increased by the surface modifications. PMID:25938725

  19. Reducing Bias Amplification in the Presence of Unmeasured Confounding Through Out-of-Sample Estimation Strategies for the Disease Risk Score

    PubMed Central

    Wyss, Richard; Lunt, Mark; Brookhart, M. Alan; Glynn, Robert J.; Stürmer, Til

    2014-01-01

    The prognostic score, or disease risk score (DRS), is a summary score that is used to control for confounding in non-experimental studies. While the DRS has been shown to effectively control for measured confounders, unmeasured confounding continues to be a fundamental obstacle in non-experimental research. Both theory and simulations have shown that in the presence of unmeasured confounding, controlling for variables that affect treatment (both instrumental variables and measured confounders) amplifies the bias caused by unmeasured confounders. In this paper, we use causal diagrams and path analysis to review and illustrate the process of bias amplification. We show that traditional estimation strategies for the DRS do not avoid bias amplification when controlling for predictors of treatment. We then discuss estimation strategies for the DRS that can potentially reduce bias amplification that is caused by controlling both instrumental variables and measured confounders. We show that under certain assumptions, estimating the DRS in populations outside the defined study cohort where treatment has not been introduced, or in outside populations with reduced treatment prevalence can control for the confounding effects of measured confounders while at the same time reduce bias amplification. PMID:25313347

  20. Autonomic Effects of Controlled Fine Particulate Exposure in Young Healthy Adults: Effect Modification by Ozone

    PubMed Central

    Fakhri, Asghar A.; Ilic, Ljubomir M.; Wellenius, Gregory A.; Urch, Bruce; Silverman, Frances; Gold, Diane R.; Mittleman, Murray A.

    2009-01-01

    Background Human controlled-exposure studies have assessed the impact of ambient fine particulate matter on cardiac autonomic function measured by heart rate variability (HRV), but whether these effects are modified by concomitant ozone exposure remains unknown. Objective In this study we assessed the impact of O3 and particulate matter exposure on HRV in humans. Methods In a crossover design, 50 subjects (19–48 years of age) were randomized to 2-hr controlled exposures to filtered air (FA), concentrated ambient particles (CAPs), O3, or combined CAPs and ozone (CAPs + O3). The primary end point was change in HRV between the start and end of exposure. Secondary analyses included blood pressure (BP) responses, and effect modification by asthmatic status. Results Achieved mean CAPs and O3 exposure concentrations were 121.6 ± 48.0 μg/m3 and 113.9 ± 6.6 ppb, respectively. In a categorical analysis, exposure had no consistent effect on HRV indices. However, the dose–response relationship between CAPs mass concentration and HRV indices seemed to vary depending on the presence of O3. This heterogeneity was statistically significant for the low-frequency component of HRV (p = 0.02) and approached significance for the high-frequency component and time-domain measures of HRV. Exposure to CAPs + O3 increased diastolic BP by 2.0 mmHg (SE, 1.2; p = 0.02). No other statistically significant changes in BP were observed. Asthmatic status did not modify these effects. Conclusion The potentiation by O3 of CAPs effects on diastolic BP and possibly HRV is of small magnitude in young adults. Further studies are needed to assess potential effects in more vulnerable populations. PMID:19672410

  1. 77 FR 59241 - Notice of Effective Date of Modifications to Certain Textile and Apparel Rules of Origin of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-26

    ... of Effective Date of Modifications to Certain Textile and Apparel Rules of Origin of the Dominican... Representative. ACTION: Notice of Effective Date of Modifications to Certain Textile and Apparel Rules of Origin...''). SUMMARY: Public Law 112-163 modified the rules of origin for certain textile and apparel goods of...

  2. The Effect of Acetaminophen on Oxidative Modification of Low-Density Lipoproteins in Hypercholesterolemic Rabbits

    PubMed Central

    Özsoy, Meral Baş; Pabuçcuoğlu, Aysun

    2007-01-01

    Oxidative modification of low-density lipoproteins (LDL) contributes to the pathology of atherosclerosis. Antioxidants may protect LDL against oxidative modification. Acetaminophen, a widely used analgesic and antipyretic agent, has significant antioxidant properties. However, there is little evidence to suggest that acetaminophen acts as an antioxidant for LDL oxidation in vivo. In this study, we investigated the in vivo effect of acetaminophen on LDL oxidation in hypercholesterolemic rabbits. The oxidative modification of LDL was identified by conjugated dienes and thiobarbituric acid-reactive substances (TBARS). In the cholesterol group which rabbits were fed a diet contained 1% g cholesterol for 8 weeks, TBARS contents and conjugated diene levels in the plasma and isolated LDL samples significantly increased compared with the control rabbits (p<0.05). However, in the cholesterol + acetaminophen group, the TBARS contents and conjugated diene levels were significantly lower than that of the cholesterol group (p<0.05). The results from in vitro studies also demonstrated that the LDL isolated from serum was oxidized by Cu++ ions and this oxidation reduced in the presence of acetaminophen. The reduced oxidative modification of LDL by acetaminophen may be of therapeutic value in preventing the development and progression of atherosclerosis. PMID:18392104

  3. Effects of Selenylation Modification on Antioxidative Activities of Schisandra chinensis Polysaccharide.

    PubMed

    Yue, Chanjuan; Chen, Jin; Hou, Ranran; Liu, Jie; Li, Xiuping; Gao, Zhenzhen; Liu, Cui; Wang, Deyun; Lu, Yu; Li, Hongquan; Hu, Yuanliang

    2015-01-01

    The selenylation modification of Schisandra chinensis polysaccharide (SCP) was conducted by the HNO3-Na2SeO3 method respectively under nine conditions according to L9(34) orthogonal design. Nine selenizing SCPs, sSCP1-sSCP9, were obtained, and their antioxidant activities were compared. In vitro test, the free radical-scavenging rates of nine sSCPs were determined for DPPH., .OH and ABTS+. sSCP1 presented the most significant effect, and could inhibit the nonenzymatic protein glycation. In vivo test, 14-day-old chickens were injected respectively with sSCP1 and SCP, the serum contents of CAT, SOD and MDA were determined. The result showed that as compared with the SCP group, the SOD and CAT activities were significantly or numerically raised and MDA content was significantly or numerically lowered in the sSCP1 group. These results indicate that selenylation modification can significantly enhance the antioxidant and antiglycative activity of SCP in vitro or in vivo. sSCP1 possesses the best efficacy and its modification conditions can be as optimal modification conditions that were 200 mg of Na2SeO3 for 500 mg of SCP, reaction temperature of 50°C and reaction time of 6 h. PMID:26230941

  4. Effects of Selenylation Modification on Antioxidative Activities of Schisandra chinensis Polysaccharide

    PubMed Central

    Yue, Chanjuan; Chen, Jin; Hou, Ranran; Liu, Jie; Li, Xiuping; Gao, Zhenzhen; Liu, Cui; Wang, Deyun; Lu, Yu; Li, Hongquan; Hu, Yuanliang

    2015-01-01

    The selenylation modification of Schisandra chinensis polysaccharide (SCP) was conducted by the HNO3–Na2SeO3 method respectively under nine conditions according to L9(34) orthogonal design. Nine selenizing SCPs, sSCP1–sSCP9, were obtained, and their antioxidant activities were compared. In vitro test, the free radical-scavenging rates of nine sSCPs were determined for DPPH., .OH and ABTS+. sSCP1 presented the most significant effect, and could inhibit the nonenzymatic protein glycation. In vivo test, 14-day-old chickens were injected respectively with sSCP1 and SCP, the serum contents of CAT, SOD and MDA were determined. The result showed that as compared with the SCP group, the SOD and CAT activities were significantly or numerically raised and MDA content was significantly or numerically lowered in the sSCP1 group. These results indicate that selenylation modification can significantly enhance the antioxidant and antiglycative activity of SCP in vitro or in vivo. sSCP1 possesses the best efficacy and its modification conditions can be as optimal modification conditions that were 200 mg of Na2SeO3 for 500 mg of SCP, reaction temperature of 50°C and reaction time of 6 h. PMID:26230941

  5. Carbon nanotubes toxicology and effects on metabolism and immunological modification in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Chiaretti, M.; Mazzanti, G.; Bosco, S.; Bellucci, S.; Cucina, A.; LeFoche, F.; Carru, G. A.; Mastrangelo, S.; Di Sotto, A.; Masciangelo, R.; Chiaretti, A. M.; Balasubramanian, C.; DeBellis, G.; Micciulla, F.; Porta, N.; Deriu, G.; Tiberia, A.

    2008-11-01

    The aim of this research is focused on the biological effects of multi wall carbon nanotubes (MWCNTs) on three different human cell types, laboratory animals in vivo, and immunological effects. Large numbers of researchers are directly involved in the handling of nanostructured materials such as MWCNTs and nanoparticles. It is important to assess the potential health risks related to their daily exposure to carbon nanotubes. The administration of sterilized nanosamples has been performed on laboratory animals, in both acute and chronic administration, and the pathological effects on the parenchymal tissues have been investigated. We studied the serum immunological modifications after intraperitoneal administration of the MWCNTs. We did not observe any antigenic reaction; the screening of ANA, anti-ENA, anti-cardiolipin, C-ANCA and P-ANCA was negative. No quantitative modification of immunoglobulins was observed, hence no modification of humoral immunity was documented. We also studied the effects of MWCNTs on the proliferation of three different cell types. MCF-7 showed a significant inhibition of proliferation for all conditions studied, whereas hSMCs demonstrated a reduction of cell growth only for the highest MWCNTs concentrations after 72 h. Also, no growth modification was observed in the Caco-2 cell line. We observed that a low quantity of MWCNTs does not provoke any inflammatory reaction. However, for future medical applications, it is important to realize prosthesis based on MWCNTs, through studying the corresponding implantation effects. Moreover, it has to be emphasized that this investigation does not address, at the moment, the carcinogenicity of MWCNTs, which requires a detailed follow-up investigation on the specific topic. In view of the subsequent and more extensive use of MWCNTs, especially in applications where carbon nanotubes are injected into the human body for drug delivery, as a contrast agent carrying entities for MRI, or as the basic

  6. The importance of scale for spatial-confounding bias and precision of spatial regression estimators

    PubMed Central

    Paciorek, Christopher J

    2010-01-01

    Residuals in regression models are often spatially correlated. Prominent examples include studies in environmental epidemiology to understand the chronic health effects of pollutants. I consider the effects of residual spatial structure on the bias and precision of regression coefficients, developing a simple framework in which to understand the key issues and derive informative analytic results. When unmeasured confounding introduces spatial structure into the residuals, regression models with spatial random effects and closely-related models such as kriging and penalized splines are biased, even when the residual variance components are known. Analytic and simulation results show how the bias depends on the spatial scales of the covariate and the residual: one can reduce bias by fitting a spatial model only when there is variation in the covariate at a scale smaller than the scale of the unmeasured confounding. I also discuss how the scales of the residual and the covariate affect efficiency and uncertainty estimation when the residuals are independent of the covariate. In an application on the association between black carbon particulate matter air pollution and birth weight, controlling for large-scale spatial variation appears to reduce bias from unmeasured confounders, while increasing uncertainty in the estimated pollution effect. PMID:21528104

  7. Effect of bentonite modification on hardness and mechanical properties of natural rubber nanocomposites

    NASA Astrophysics Data System (ADS)

    Santiago, Denise Ester O.; Pajarito, Bryan B.; Mangaccat, Winna Faye F.; Tigue, Maelyn Rose M.; Tipton, Monica T.

    2016-05-01

    The effect of sodium activation, ion-exchange with tertiary amine salt, surface treatment with non-ionic surfactant, and wet grinding of bentonite on hardness and mechanical properties of natural rubber nanocomposites (NRN) was studied using full factorial design of experiment. Results of X-ray diffraction (XRD) show increase in basal spacing d of bentonite due to modification, while attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) confirm the organic modification of bentonite. Analysis of variance (ANOVA) shows that the main effect of surface treatment increases the hardness and decreases the tensile modulus of the NRN. The surface treatment and wet grinding of bentonite decrease the tensile stresses at 100, 200 and 300% strain of NRN. Sodium activation and ion-exchange negatively affect the compressive properties, while surface treatment significantly improves the compressive properties of NRN.

  8. Heat Waves in the United States: Mortality Risk during Heat Waves and Effect Modification by Heat Wave Characteristics in 43 U.S. Communities

    PubMed Central

    Anderson, G. Brooke; Bell, Michelle L.

    2011-01-01

    Background Devastating health effects from recent heat waves, and projected increases in frequency, duration, and severity of heat waves from climate change, highlight the importance of understanding health consequences of heat waves. Objectives We analyzed mortality risk for heat waves in 43 U.S. cities (1987–2005) and investigated how effects relate to heat waves’ intensity, duration, or timing in season. Methods Heat waves were defined as ≥ 2 days with temperature ≥ 95th percentile for the community for 1 May through 30 September. Heat waves were characterized by their intensity, duration, and timing in season. Within each community, we estimated mortality risk during each heat wave compared with non-heat wave days, controlling for potential confounders. We combined individual heat wave effect estimates using Bayesian hierarchical modeling to generate overall effects at the community, regional, and national levels. We estimated how heat wave mortality effects were modified by heat wave characteristics (intensity, duration, timing in season). Results Nationally, mortality increased 3.74% [95% posterior interval (PI), 2.29–5.22%] during heat waves compared with non-heat wave days. Heat wave mortality risk increased 2.49% for every 1°F increase in heat wave intensity and 0.38% for every 1-day increase in heat wave duration. Mortality increased 5.04% (95% PI, 3.06–7.06%) during the first heat wave of the summer versus 2.65% (95% PI, 1.14–4.18%) during later heat waves, compared with non-heat wave days. Heat wave mortality impacts and effect modification by heat wave characteristics were more pronounced in the Northeast and Midwest compared with the South. Conclusions We found higher mortality risk from heat waves that were more intense or longer, or those occurring earlier in summer. These findings have implications for decision makers and researchers estimating health effects from climate change. PMID:21084239

  9. Prenatal Paracetamol Exposure and Wheezing in Childhood: Causation or Confounding?

    PubMed Central

    Migliore, Enrica; Zugna, Daniela; Galassi, Claudia; Merletti, Franco; Gagliardi, Luigi; Rasero, Laura; Trevisan, Morena; Rusconi, Franca; Richiardi, Lorenzo

    2015-01-01

    Background Several studies have reported an increased risk of wheezing in the children of mothers who used paracetamol during pregnancy. We evaluated to what extent this association is explained by confounding. Methods We investigated the association between maternal paracetamol use in the first and third trimester of pregnancy and ever wheezing or recurrent wheezing/asthma in infants in the NINFEA cohort study. Risks ratios (RR) and 95% confidence intervals (CI) were estimated after adjustment for confounders, including maternal infections and antibiotic use during pregnancy. Results The prevalence of maternal paracetamol use was 30.6% during the first and 36.7% during the third trimester of pregnancy. The prevalence of ever wheezing and recurrent wheezing/asthma was 16.9% and 5.6%, respectively. After full adjustment, the RR for ever wheezing decreased from 1.25 [1.07–1.47] to 1.10 [0.94–1.30] in the first, and from 1.26 [1.08–1.47] to 1.10 [0.93–1.29] in the third trimester. A similar pattern was observed for recurrent wheezing/asthma. Duration of maternal paracetamol use was not associated with either outcome. Further analyses on paracetamol use for three non-infectious disorders (sciatica, migraine, and headache) revealed no increased risk of wheezing in children. Conclusion The association between maternal paracetamol use during pregnancy and infant wheezing is mainly, if not completely explained by confounding. PMID:26305473

  10. Mediation Analysis With Intermediate Confounding: Structural Equation Modeling Viewed Through the Causal Inference Lens

    PubMed Central

    De Stavola, Bianca L.; Daniel, Rhian M.; Ploubidis, George B.; Micali, Nadia

    2015-01-01

    The study of mediation has a long tradition in the social sciences and a relatively more recent one in epidemiology. The first school is linked to path analysis and structural equation models (SEMs), while the second is related mostly to methods developed within the potential outcomes approach to causal inference. By giving model-free definitions of direct and indirect effects and clear assumptions for their identification, the latter school has formalized notions intuitively developed in the former and has greatly increased the flexibility of the models involved. However, through its predominant focus on nonparametric identification, the causal inference approach to effect decomposition via natural effects is limited to settings that exclude intermediate confounders. Such confounders are naturally dealt with (albeit with the caveats of informality and modeling inflexibility) in the SEM framework. Therefore, it seems pertinent to revisit SEMs with intermediate confounders, armed with the formal definitions and (parametric) identification assumptions from causal inference. Here we investigate: 1) how identification assumptions affect the specification of SEMs, 2) whether the more restrictive SEM assumptions can be relaxed, and 3) whether existing sensitivity analyses can be extended to this setting. Data from the Avon Longitudinal Study of Parents and Children (1990–2005) are used for illustration. PMID:25504026

  11. Effects of Surface Modification Conditions on Hydrophobicity of Silica-based Coating Additives

    SciTech Connect

    Armstrong, Beth L; Pawel, Steven J; Hunter, Scott Robert; Haynes, James A; Hillesheim, Daniel A

    2013-01-01

    Superhydrophobic silica (SHS) powders are being evaluated as a potential additive to the polyurethane topcoats used in Chemical Agent Resistant Coating (CARC) systems, with the goal of improving water repellency and corrosion protection characteristics. The current generation of CARC topcoats is already highly loaded with solids, and thus there is a premium on minimization of the total SHS powder required to achieve the desired properties. Therefore, efficient surface modification of the silica and proper dispersion in the coating will be required. The effect of a dispersant on the surface modification of silica particles by chlorosilanes was addressed in this study. The properties of various SHS powders were characterized by thermogravimetric analysis and mass spectroscopy. Correlations between powder modification conditions and the ultimate effects of the modified particles on hydrophobicity of CARC topcoats were assessed. The use of contact and rolling angle measurements along with scanning electron microscopy are discussed as they pertain to the ability to quantify the effects of modified silicas on corrosion prevention coatings. Furthermore, a systematic approach to modifying and testing both powders and top coats of corrosion prevention systems is presented.

  12. Effect of substituents and structural modification on conformational equilibrium in bis-quinolizidine system

    NASA Astrophysics Data System (ADS)

    Wysocka, Waleria; Brukwicki, Tadeusz; Włodarczak, Jacek

    2012-06-01

    On the basis of literature interpretation of 13C NMR and 1H NMR spectra of bis-quinolizidine alkaloids, the values of free enthalpy ΔG of conformational equilibria of those compounds were calculated. The results were analysed together with the X-ray and DFT data to discuss the effects of different substituents attached to the sparteine system in various positions as well as the effects of structural modifications on conformational equilibria. The measure of the effect was expressed by ΔΔG value, defined as the difference in ΔG of the compound under consideration and its parent compound without a given substituent.

  13. Threats to internal validity in exercise science: a review of overlooked confounding variables.

    PubMed

    Halperin, Israel; Pyne, David B; Martin, David T

    2015-10-01

    Internal validity refers to the degree of control exerted over potential confounding variables to reduce alternative explanations for the effects of various treatments. In exercise and sports-science research and routine testing, internal validity is commonly achieved by controlling variables such as exercise and warm-up protocols, prior training, nutritional intake before testing, ambient temperature, time of testing, hours of sleep, age, and gender. However, a number of other potential confounding variables often do not receive adequate attention in sports physiology and performance research. These confounding variables include instructions on how to perform the test, volume and frequency of verbal encouragement, knowledge of exercise endpoint, number and gender of observers in the room, influence of music played before and during testing, and the effects of mental fatigue on performance. In this review the authors discuss these variables in relation to common testing environments in exercise and sports science and present some recommendations with the goal of reducing possible threats to internal validity. PMID:25756869

  14. Effects of oxidative modification on thermal aggregation and gel properties of soy protein by malondialdehyde.

    PubMed

    Wu, Wei; Hua, Yufei; Lin, Qinlu

    2014-03-01

    Malondialdehyde (MDA) was selected as a representative of lipid peroxidation products to investigate the effects of oxidative modification on thermal aggregation and gel properties of soy protein by lipid peroxidation products. Incubation of soy protein with increasing concentration of MDA resulted in gradual decrease of particle size and content of thermal aggregates during heat denaturation. Oxidative modification by MDA resulted in a decrease in water holding capacity, gel hardness, and gel strength of soy protein gel. An increase in coarseness and interstice of MDA modified protein gel network was accompanied by uneven distribution of interstice as MDA concentration increased. The results showed that degree of thermal aggregation of MDA-modified soy protein gradually decreased as MDA concentration increased, which contributed to a decrease in water holding capacity, gel hardness, and gel strength of MDA-modified soy protein gel. PMID:24587523

  15. The effects of equipment modification on children's self-efficacy and basketball shooting performance.

    PubMed

    Chase, M A; Ewing, M E; Lirgg, C D; George, T R

    1994-06-01

    The purpose of this study was to examine the effects of modification of basketball size and basket height on shooting performance and self-efficacy of girls and boys 9 to 12 years of age. Subjects (N = 74) completed a self-efficacy questionnaire before and after shooting 10 baskets under four conditions. Shooting conditions were a combination of basketball size (women's or men's) and basket height (10 or 8 ft). Repeated measures analyses of variance indicated that children made more baskets and had higher shooting scores at the 8-ft basket than the 10-ft basket. This was especially evident for girls and 9- and 10-year-old children. Self-efficacy was higher prior to shooting, and boys had higher self-efficacy than girls. Self-efficacy was highest when children shot at the 8-ft basket. These results indicated that basket height modification can positively influence children's shooting performance and self-efficacy. PMID:8047708

  16. Structual Effects of Cytidine 2^' Ribose Modifications as Determined by Irmpd Action Spectroscopy

    NASA Astrophysics Data System (ADS)

    Hamlow, Lucas; He, Chenchen; Fan, Lin; Wu, Ranran; Yang, Bo; Rodgers, M. T.; Berden, Giel; Oomens, J.

    2015-06-01

    Modified nucleosides, both naturally occurring and synthetic play an important role in understanding and manipulating RNA and DNA. Naturally occurring modified nucleosides are commonly found in functionally important regions of RNA and also affect antibiotic resistance or sensitivity. Synthetic modifications of nucleosides such as fluorinated and arabinosyl nucleosides have found uses as anti-virals and chemotherapy agents. Understanding the effect that modifications have on structure and glycosidic bond stability may lend insight into the functions of these modified nucleosides. Modifications such as the naturally occurring 2^'-O-methylation and the synthetic 2^'-fluorination are believed to help stabilize the nucleoside through the glycosidic bond stability and intramolecular hydrogen bonding. Changing the sugar from ribose to arabinose alters the stereochemistry at the 2^' position and thus shifts the 3D orientation of the 2^'-hydroxyl group, which also affects intramolecular hydrogen bonding and glycosidic bond stability. The structures of 2^'-deoxy-2^'-fluorocytidine, 2^'-O-methylcytidine and cytosine arabinoside are examined in the current work by measuring the infrared spectra in the IR fingerprint region using infrared multiple photon dissociation (IRMPD) action spectroscopy. The structures accessed in the experiments were determined via comparison of the measured IRMPD action spectra to the theoretical linear IR spectra determined by density functional theory and molecular modeling for the stable low-energy structures. Although glycosidic bond stability cannot be quantitatively determined from this data, complementary TCID studies will establish the effect of these modifications. Comparison of these modified nucleosides with their RNA and DNA analogues will help elucidate differences in their intrinsic chemistry.

  17. Effects of tooth profile modification on dynamic responses of a high speed gear-rotor-bearing system

    NASA Astrophysics Data System (ADS)

    Hu, Zehua; Tang, Jinyuan; Zhong, Jue; Chen, Siyu; Yan, Haiyan

    2016-08-01

    A finite element node dynamic model of a high speed gear-rotor-bearing system considering the time-varying mesh stiffness, backlash, gyroscopic effect and transmission error excitation is developed. Different tooth profile modifications are introduced into the gear pair and corresponding time-varying mesh stiffness curves are obtained. Effects of the tooth profile modification on mesh stiffness are analyzed, and the natural frequencies and mode shapes of the gear-rotor-bearing transmission system are given. The dynamic responses with respect to a wide input speed region including dynamic factor, vibration amplitude near the bearing and dynamic transmission error are obtained by introducing the time-varying mesh stiffness in different tooth profile modification cases into the gear-rotor-bearing dynamic system. Effects of the tooth profile modification on the dynamic responses are studied in detail. The numerical simulation results show that both the short profile modification and the long profile modification can affect the mutation of the mesh stiffness when the number of engaging tooth pairs changes. A short profile modification with an appropriate modification amount can improve the dynamic property of the system in certain work condition.

  18. Treatment Modifications and Treatment-Limiting Toxicities or Side Effects: Risk Factors and Temporal Trends.

    PubMed

    Pantazis, Nikos; Psichogiou, Mina; Paparizos, Vassilios; Gargalianos, Panagiotis; Chini, Maria; Protopapas, Konstantinos; Sipsas, Nikolaos V; Panos, George; Chrysos, George; Sambatakou, Helen; Katsarou, Olga; Touloumi, Giota

    2015-07-01

    Combined antiretroviral treatment (cART) modifications are often required due to treatment failure or side effects. We investigate cART regimens' durability, frequency of treatment-limiting adverse events, and potential risk factors and temporal trends. Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). Statistical analyses were based on survival techniques, allowing for multiple contributions per individual. Overall, 2,756 individuals, aged >15 years, initiated cART. cART regimens were grouped by their initiation date into four calendar periods (1995-1998, 1999-2002, 2003-2006, and 2007+). Median [95% confidence interval (CI)] time to first treatment modification was 2.11 (1.95-2.33) years; cumulative probabilities at 1 year were 31.6%, 29.0%, 33.1%, and 29.6% for the four periods, respectively. cART modifications were less frequent in more recent years (adjusted HR=0.96 per year; p<0.001). Longer treatment duration was associated with lower HIV-RNA, higher CD4 counts, and being previously ART naive. cART modifications due to treatment failure became less frequent in recent years (adjusted HR=0.91 per year; p<0.001). Estimated (95% CI) 1 year cumulative probabilities of treatment-limiting side effects were 16.4% (12.0-21.3%), 19.3% (15.6-23.3%), 24.9% (20.3-29.7%), and 21.1% (13.4-29.9%) for the four periods, respectively, with no significant temporal trends. Risk of side effects was lower in nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens or triple nucleoside reverse transcriptase inhibitor (NRTI)-based cART regimens. Treatment modifications have become less frequent in more recent years. This could be partly attributed to the lower risk for side effects of NNRTI-based cART regimens and mainly to the improved efficacy of newer drugs. However, the rate of drugs substitutions due to adverse events remains substantially high. PMID:25950848

  19. An assessment of the possible extent of confounding in epidemiological studies of lung cancer risk among roofers

    SciTech Connect

    Mundt, D.J.; van Wijngaarden, E.; Mundt, K.A.

    2007-07-01

    We evaluated the likelihood and extent to which the observed increased risk of lung cancer may be due to confounding (a mixing of effects of multiple exposures) by co-exposure to other potential carcinogens present in roofing or to lifestyle variables. We conducted a review of the epidemiological and industrial hygiene literature of asphalt-exposed workers. Peer-reviewed epidemiological studies of asphalt fumes, related occupational exposures, and confounding factors were identified from MEDLINE (1966 early 2004). Industrial hygiene studies of asphalt workers were identified through MEDLINE, publicly available government documents, and asphalt industry documents. Using well established statistical methods, we quantified the extent to which lung cancer relative risk estimates among roofers reflect confounding from other exposures, using different prevalence and risk scenarios. The relative risk of lung cancer varied from 1.2 to 5.0 in 13 epidemiological studies of roofers; most studies reported a relative risk between 1.2 and 1.4. Smoking, asbestos and coal tar were the most likely confounders, but the prevalence of these factors varied over time. The results of the study indicate that much of the observed risk reported in epidemiological studies of cancer among roofers is well within the range of what may have resulted from confounding by reasonable and expected levels of smoking, asbestos or coal tar. This may be particularly true for those studies that did not adjust for these confounders and where the exposure was defined as employment in the roofing industry. In addition to poorly defined asphalt exposure, uncontrolled confounding cannot reliably be ruled out in studies of lung cancer among asphalt-exposed roofers. Therefore, it is not possible to conclude whether roofers are at increased risk of lung cancer due to asphalt exposure.

  20. Reporting phenotypes in mouse models when considering body size as a potential confounder.

    PubMed

    Oellrich, Anika; Meehan, Terrence F; Parkinson, Helen; Sarntivijai, Sirarat; White, Jacqueline K; Karp, Natasha A

    2016-01-01

    Genotype-phenotype studies aim to identify causative relationships between genes and phenotypes. The International Mouse Phenotyping Consortium is a high throughput phenotyping program whose goal is to collect phenotype data for a knockout mouse strain of every protein coding gene. The scale of the project requires an automatic analysis pipeline to detect abnormal phenotypes, and disseminate the resulting gene-phenotype annotation data into public resources. A body weight phenotype is a common result of knockout studies. As body weight correlates with many other biological traits, this challenges the interpretation of related gene-phenotype associations. Co-correlation can lead to gene-phenotype associations that are potentially misleading. Here we use statistical modelling to account for body weight as a potential confounder to assess the impact. We find that there is a considerable impact on previously established gene-phenotype associations due to an increase in sensitivity as well as the confounding effect. We investigated the existing ontologies to represent this phenotypic information and we explored ways to ontologically represent the results of the influence of confounders on gene-phenotype associations. With the scale of data being disseminated within the high throughput programs and the range of downstream studies that utilise these data, it is critical to consider how we improve the quality of the disseminated data and provide a robust ontological representation. PMID:26865945

  1. The effect of hypusine modification on the intracellular localization of eIF5A

    PubMed Central

    Lee, Seung Bum; Park, Jong Hwan; Kaevel, Jorn; Sramkova, Monika; Weigert, Roberto; Park, Myung Hee

    2009-01-01

    Eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein essential for eukaryotic cell proliferation and is the only protein containing hypusine, [Nε-(4-amino-2-hydroxybutyl)lysine]. eIF5A is activated by the posttranslational synthesis of hypusine. eIF5A also undergoes an acetylation at specific Lys residue(s). In this study, we have investigated the effect of hypusine modification and acetylation on the subcellular localization of eIF5A. Immunocytochemical analyses showed differences in the distribution of non-hypusinated eIF5A precursor and the hypusine-containing mature eIF5A. While the precursor is found in both cytoplasm and nucleus, the hypusinated eIF5A is primarily localized in cytoplasm. eIF5A mutant proteins, defective in hypusine modification (K50A, K50R) were localized in a similar manner to the eIF5A precursor, whereas hypusine-modified mutant proteins (K47A, K47R, K68A) were localized mainly in the cytoplasm. These findings provide strong evidence that the hypusine modification of eIF5A dictates its localization in the cytoplasmic compartment where it is required for protein synthesis. PMID:19379712

  2. The effect of hypusine modification on the intracellular localization of eIF5A

    SciTech Connect

    Lee, Seung Bum; Park, Jong Hwan; Kaevel, Joern; Sramkova, Monika; Weigert, Roberto; Park, Myung Hee

    2009-06-12

    Eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein essential for eukaryotic cell proliferation and is the only protein containing hypusine, [N{sup {epsilon}}-(4-amino-2-hydroxybutyl)lysine]. eIF5A is activated by the post-translational synthesis of hypusine. eIF5A also undergoes an acetylation at specific Lys residue(s). In this study, we have investigated the effect of hypusine modification and acetylation on the subcellular localization of eIF5A. Immunocytochemical analyses showed differences in the distribution of non-hypusinated eIF5A precursor and the hypusine-containing mature eIF5A. While the precursor is found in both cytoplasm and nucleus, the hypusinated eIF5A is primarily localized in cytoplasm. eIF5A mutant proteins, defective in hypusine modification (K50A, K50R) were localized in a similar manner to the eIF5A precursor, whereas hypusine-modified mutant proteins (K47A, K47R, K68A) were localized mainly in the cytoplasm. These findings provide strong evidence that the hypusine modification of eIF5A dictates its localization in the cytoplasmic compartment where it is required for protein synthesis.

  3. Effect of Atmospheric Pressure Plasma Modification on Polyimide and Adhesive Joining with Titanium

    NASA Astrophysics Data System (ADS)

    Akram, M.; Jansen, K. M. B.; Ernst, L. J.; Bhowmik, S.; Ajeesh, G.; Ahmed, S.; Chakraborty, D.

    2015-10-01

    This investigation highlights the effect of surface modification on polyimide by atmospheric pressure plasma treatment with different exposure time. Surface modification of polymer by plasma treatment essentially creates physical and chemical changes such as cross-linking and formation of free radicals. It also forms oxygen functionalization in the form of polar groups on polymer surface, hence improving the wetting and adhesion properties. It is observed that surface energy of the polymer increases with increasing exposure time of atmospheric pressure plasma. However, prolonged exposure time of plasma results in deterioration of the surface layer of polyimide resulting in degradation and embrittlement. Scanning electron microscopy and atomic force microscopy analysis reveal that there is a considerable morphological change on the polymer surface due to atmospheric pressure plasma treatment. X-ray photo electron spectroscopy analysis reveals that the oxygen functionalities of polymer surface increases significantly when polyimide is exposed to atmospheric pressure plasma. Untreated and atmospheric pressure plasma-treated polyimide sheet are adhesive bonded by employing polyimide adhesive as well as with titanium substrate. Due to surface modification of polyimide, it is observed that there is a significant increase in lap shear tensile strength, and therefore, this technology is highly acceptable for aviation and space applications.

  4. Effect of Lysine Modification on the Stability and Cellular Binding of Human Amyloidogenic Light Chains

    SciTech Connect

    O'Neill, Hugh Michael; Davern, Sandra M.; Murphy, Charles L.; Wall, Jonathan; Deborah, Weiss T.; Solomon, Alan

    2011-01-01

    AL amyloidosis is characterized by the pathologic deposition as fibrils of monoclonal light chains (i.e., Bence Jones proteins [BJPs]) in particular organs and tissues. This phenomenon has been attributed to the presence in amyloidogenic proteins of particular amino acids that cause these molecules to become unstable, as well as post-translational modifications and, in regard to the latter, we have investigated the effect of biotinylation of lysyl residues on cell binding. We utilized an experimental system designed to test if BJPs obtained from patients with AL amyloidosis or, as a control, multiple myeloma (MM), bound human fibroblasts and renal epithelial cells. As documented by fluorescent microscopy and ELISA, the amyloidogenic BJPs, as compared with MM components, bound preferentially and this reactivity increased significantly after chemical modification of their lysyl residues with sulfo-NHS-biotin. Further, based on tryptophan fluorescence and circular dichorism data, it was apparent that their conformation was altered, which we hypothesize exposed a binding site not accessible on the native protein. The results of our studies indicate that post-translational structural modifications of pathologic light chains can enhance their capacity for cellular interaction and thus may contribute to the pathogenesis of AL amyloidosis and multiple myeloma.

  5. Evaluating Public Health Interventions: 3. The Two-Stage Design for Confounding Bias Reduction—Having Your Cake and Eating It Two

    PubMed Central

    Spiegelman, Donna; Rivera-Rodriguez, Claudia L.; Haneuse, Sebastien

    2016-01-01

    In public health evaluations, confounding bias in the estimate of the intervention effect will typically threaten the validity of the findings. It is a common misperception that the only way to avoid this bias is to measure detailed, high-quality data on potential confounders for every intervention participant, but this strategy for adjusting for confounding bias is often infeasible. Rather than ignoring confounding altogether, the two-phase design and analysis—in which detailed high-quality confounding data are obtained among a small subsample—can be considered. We describe the two-stage design and analysis approach, and illustrate its use in the evaluation of an intervention conducted in Dar es Salaam, Tanzania, of an enhanced community health worker program to improve antenatal care uptake. PMID:27285260

  6. Evaluating Public Health Interventions: 3. The Two-Stage Design for Confounding Bias Reduction-Having Your Cake and Eating It Two.

    PubMed

    Spiegelman, Donna; Rivera-Rodriguez, Claudia L; Haneuse, Sebastien

    2016-07-01

    In public health evaluations, confounding bias in the estimate of the intervention effect will typically threaten the validity of the findings. It is a common misperception that the only way to avoid this bias is to measure detailed, high-quality data on potential confounders for every intervention participant, but this strategy for adjusting for confounding bias is often infeasible. Rather than ignoring confounding altogether, the two-phase design and analysis-in which detailed high-quality confounding data are obtained among a small subsample-can be considered. We describe the two-stage design and analysis approach, and illustrate its use in the evaluation of an intervention conducted in Dar es Salaam, Tanzania, of an enhanced community health worker program to improve antenatal care uptake. PMID:27285260

  7. Differential effects of cocaine on histone posttranslational modifications in identified populations of striatal neurons.

    PubMed

    Jordi, Emmanuelle; Heiman, Myriam; Marion-Poll, Lucile; Guermonprez, Pierre; Cheng, Shuk Kei; Nairn, Angus C; Greengard, Paul; Girault, Jean-Antoine

    2013-06-01

    Drugs of abuse, such as cocaine, induce changes in gene expression and epigenetic marks including alterations in histone posttranslational modifications in striatal neurons. These changes are thought to participate in physiological memory mechanisms and to be critical for long-term behavioral alterations. However, the striatum is composed of multiple cell types, including two distinct populations of medium-sized spiny neurons, and little is known concerning the cell-type specificity of epigenetic modifications. To address this question we used bacterial artificial chromosome transgenic mice, which express EGFP fused to the N-terminus of the large subunit ribosomal protein L10a driven by the D1 or D2 dopamine receptor (D1R, D2R) promoter, respectively. Fluorescence in nucleoli was used to sort nuclei from D1R- or D2R-expressing neurons and to quantify by flow cytometry the cocaine-induced changes in histone acetylation and methylation specifically in these two types of nuclei. The two populations of medium-sized spiny neurons displayed different patterns of histone modifications 15 min or 24 h after a single injection of cocaine or 24 h after seven daily injections. In particular, acetylation of histone 3 on Lys 14 and of histone 4 on Lys 5 and 12, and methylation of histone 3 on Lys 9 exhibited distinct and persistent changes in the two cell types. Our data provide insights into the differential epigenetic responses to cocaine in D1R- and D2R-positive neurons and their potential regulation, which may participate in the persistent effects of cocaine in these neurons. The method described should have general utility for studying nuclear modifications in different types of neuronal or nonneuronal cell types. PMID:23690581

  8. Thermal effects on the Ga+ ion beam induced structural modification of a-SiC:H

    NASA Astrophysics Data System (ADS)

    Tsvetkova, T.; Wright, C. D.; Craciun, M. F.; Bischoff, L.; Angelov, O.; Dimova-Malinovska, D.

    2012-12-01

    The effects of implantation temperature and post-implantation thermal annealing on the Ga+ ion beam induced optical contrast formation in hydrogenated silicon-carbon alloy (a-SiC:H) films and underlying structural modifications have been studied. The optical contrast formed (between implanted and unimplanted regions of the film material) has been made use of in the form of optical pattern formation by computer-operated Ga+-focused ion beam. Possible applications of this effect in the area of submicron lithography and high-density optical data storage have been suggested with regard to the most widely spread focused micro-beam systems based on Ga+ liquid metal ion sources. The implanted samples were structurally analysed using vibrational spectroscopies, like Raman and infra-red (IR) spectroscopy, to define optimum implantation conditions. The precise role of implantation temperature effects, i.e. the target temperature during Ga+ ion irradiation, on the structural modification obtainable has been therefore a key part of this study. Appropriate post-implantation annealing treatments were also studied, since these are expected to offer further benefits in reducing the required ion dose and enhancing the optical contrast, thus increasing the cost-effectiveness of the method.

  9. Position-dependent performance of copper phthalocyanine based field-effect transistors by gold nanoparticles modification.

    PubMed

    Luo, Xiao; Li, Yao; Lv, Wenli; Zhao, Feiyu; Sun, Lei; Peng, Yingquan; Wen, Zhanwei; Zhong, Junkang; Zhang, Jianping

    2015-01-21

    A facile fabrication and characteristics of copper phthalocyanine (CuPc)-based organic field-effect transistor (OFET) using the gold nanoparticles (Au NPs) modification is reported, thereby achieving highly improved performance. The effect of Au NPs located at three different positions, that is, at the SiO2/CuPc interface (device B), embedding in the middle of CuPc layer (device C), and on the top of CuPc layer (device D), is investigated, and the results show that device D has the best performance. Compared with the device without Au NPs (reference device A), device D displays an improvement of field-effect mobility (μ(sat)) from 1.65 × 10(-3) to 5.51 × 10(-3) cm(2) V(-1) s(-1), and threshold voltage decreases from -23.24 to -16.12 V. Therefore, a strategy for the performance improvement of the CuPc-based OFET with large field-effect mobility and saturation drain current is developed, on the basis of the concept of nanoscale Au modification. The model of an additional electron transport channel formation by FET operation at the Au NPs/CuPc interface is therefore proposed to explain the observed performance improvement. Optimum CuPc thickness is confirmed to be about 50 nm in the present study. The device-to-device uniformity and time stability are discussed for future application. PMID:25548878

  10. External Adjustment Sensitivity Analysis for Unmeasured Confounding: An Application to Coronary Stent Outcomes, Pennsylvania 2004–2008

    PubMed Central

    Huesch, Marco D

    2013-01-01

    Background Assessing the real-world comparative effectiveness of common interventions is challenged by unmeasured confounding. Objective To determine whether the mortality benefit shown for drug-eluting stents (DES) over bare metal stents (BMS) in observational studies persists after controls for/tests for confounding. Data Sources/Study Setting Retrospective observational study involving 38,019 patients, 65 years or older admitted for an index percutaneous coronary intervention receiving DES or BMS in Pennsylvania in 2004–2005 followed up for death through 3 years. Study Design Analysis was at the patient level. Mortality was analyzed with Cox proportional hazards models allowing for stratification by disease severity or DES use propensity, accounting for clustering of patients. Instrumental variables analysis used lagged physician stent usage to proxy for the focal stent type decision. A method originating in work by Cornfield and others in 1954 and popularized by Greenland in 1996 was used to assess robustness to confounding. Principal Findings DES was associated with a significantly lower adjusted risk of death at 3 years in Cox and in instrumented analyses. An implausibly strong hypothetical unobserved confounder would be required to fully explain these results. Conclusions Confounding by indication can bias observational studies. No strong evidence of such selection biases was found in the reduced risk of death among elderly patients receiving DES instead of BMS in a Pennsylvanian state-wide population. PMID:23206261

  11. Soil modification by invasive plants: Effects on native and invasive species of mixed-grass prairies

    USGS Publications Warehouse

    Jordan, N.R.; Larson, D.L.; Huerd, S.C.

    2008-01-01

    Invasive plants are capable of modifying attributes of soil to facilitate further invasion by conspecifics and other invasive species. We assessed this capability in three important plant invaders of grasslands in the Great Plains region of North America: leafy spurge (Euphorbia esula), smooth brome (Bromus inermis) and crested wheatgrass (Agropyron cristatum). In a glasshouse, these three invasives or a group of native species were grown separately through three cycles of growth and soil conditioning in both steam-pasteurized and non-pasteurized soils, after which we assessed seedling growth in these soils. Two of the three invasive species, Bromus and Agropyron, exhibited significant self-facilitation via soil modification. Bromus and Agropyron also had significant facilitative effects on other invasives via soil modification, while Euphorbia had significant antagonistic effects on the other invasives. Both Agropyron and Euphorbia consistently suppressed growth of two of three native forbs, while three native grasses were generally less affected. Almost all intra- and interspecific effects of invasive soil conditioning were dependent upon presence of soil biota from field sites where these species were successful invaders. Overall, these results suggest that that invasive modification of soil microbiota can facilitate plant invasion directly or via 'cross-facilitation' of other invasive species, and moreover has potential to impede restoration of native communities after removal of an invasive species. However, certain native species that are relatively insensitive to altered soil biota (as we observed in the case of the forb Linum lewisii and the native grasses), may be valuable as 'nurse'species in restoration efforts. ?? 2007 Springer Science+Business Media B.V.

  12. Processed Pseudogene Confounding Deletion/Duplication Assays for SMAD4.

    PubMed

    Millson, Alison; Lewis, Tracey; Pesaran, Tina; Salvador, David; Gillespie, Katrina; Gau, Chia-Ling; Pont-Kingdon, Genevieve; Lyon, Elaine; Bayrak-Toydemir, Pinar

    2015-09-01

    Mutations in SMAD4 have been associated with juvenile polyposis syndrome and combined juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome. SMAD4 is part of the SMAD gene family. To date, there has been no report in the literature of a SMAD4 pseudogene. An unusual SMAD4 duplication pattern was seen in multiple patient samples using two different duplication/deletion platforms: multiplex ligation-dependent probe amplification and chromosomal microarray. Follow-up confirmatory testing included real-time quantitative PCR and sequencing of an exon/exon junction, all results leading to the conclusion of the existence of a processed pseudogene. Examination of clinical results from two laboratories found a frequency of 0.26% (12 in 4672 cases) for this processed pseudogene. This is the first report of the presence of a processed pseudogene for SMAD4. We believe that knowledge of its existence is important for accurate interpretation of clinical diagnostic test results and for new assay designs. This study also indicates how a processed pseudogene may confound quantitative results, dependent on placement of probes and/or primers in a particular assay design, potentially leading to both false-positive and false-negative results. We also found that the SMAD4 processed pseudogene affects next-generation sequencing results by confounding the alignment of the sequences, resulting in erroneous variant calls. We recommend Sanger sequencing confirmation for SMAD4 variants. PMID:26165824

  13. The effect of decitabine dose modification and myelosuppression on response and survival in patients with myelodysplastic syndromes.

    PubMed

    Jabbour, Elias; Garcia-Manero, Guillermo; Cornelison, A Megan; Cortes, Jorge E; Ravandi, Farhad; Daver, Naval; Kadia, Tapan; Teng, Angela; Kantarjian, Hagop

    2015-02-01

    Myelosuppression in myelodysplastic syndromes (MDS) is associated with the hypomethylating agent decitabine. A retrospective pooled analysis of two decitabine clinical trials in patients with MDS conducted Cox regression analyses of red blood cell or platelet dependence, myelosuppression, dose modification, cycle delay or dose reduction, and survival effects. In 182 patients, baseline platelet dependence was a predictor for dose modification, reduction or delay, and death (modification: p=0.006, hazard ratio [HR]=2.04; reduction/delay: p=0.011, HR=2.00; death: p=0.003, HR=1.94). Patients with dose modifications had significantly higher overall response rates versus those with none (22% vs. 10%; p=0.015). Patients with no dose modifications had faster progression to acute myeloid leukemia (AML) versus patients with dose modifications (p=0.004). Without dose modifications, patients tended to drop out due to disease progression or other reasons. Decitabine dose modifications on treatment may indicate response to treatment. PMID:24844364

  14. New Ion Beam Materials Laboratory for Materials Modification and Irradiation Effects Research

    SciTech Connect

    Zhang, Yanwen; Crespillo, Miguel L; Xue, Haizhou; Jin, Ke; Chen, Chien-Hung; Fontana, Cristiano L; Graham, Dr. Joseph T.; Weber, William J

    2014-11-01

    A new multifunctional ion beam materials laboratory (IBML) has been established at the University of Tennessee, in partnership with Oak Ridge National Laboratory. The IBML is currently equipped with two ion sources, a 3 MV tandem accelerator, three beamlines and three endstations. The IBML is primarily dedicated to fundamental research on ion-solid interaction, ion beam analysis, ion beam modification, and other basic and applied research on irradiation effects in a wide range of materials. An overview of the IBML facility is provided, and experimental results are reported to demonstrate the specific capabilities.

  15. New ion beam materials laboratory for materials modification and irradiation effects research

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Crespillo, M. L.; Xue, H.; Jin, K.; Chen, C. H.; Fontana, C. L.; Graham, J. T.; Weber, W. J.

    2014-11-01

    A new multifunctional ion beam materials laboratory (IBML) has been established at the University of Tennessee, in partnership with Oak Ridge National Laboratory. The IBML is currently equipped with two ion sources, a 3 MV tandem accelerator, three beamlines and three endstations. The IBML is primarily dedicated to fundamental research on ion-solid interaction, ion beam analysis, ion beam modification, and other basic and applied research on irradiation effects in a wide range of materials. An overview of the IBML facility is provided, and experimental results are reported to demonstrate the specific capabilities.

  16. Quantification of Treatment Effect Modification on Both an Additive and Multiplicative Scale

    PubMed Central

    Girerd, Nicolas; Rabilloud, Muriel; Pibarot, Philippe; Mathieu, Patrick; Roy, Pascal

    2016-01-01

    Background In both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinical events. Methods The effect of treatment and the effect modification of treatment were respectively assessed using a multiplicative and an additive hazard model in an analysis adjusted for propensity score in the context of coronary surgery. Results The multiplicative model yielded a lower relative hazard reduction with bilateral internal thoracic artery grafting in older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p = 0.05) whereas the additive model reported a similar absolute hazard reduction with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p = 0.61). The number needed to treat derived from the propensity score-adjusted multiplicative model was remarkably similar at the end of the follow-up in patients aged < = 60 and in patients >70. Conclusions The present example demonstrates that a lower treatment effect in older patients on a relative scale can conversely translate into a similar treatment effect on an additive scale due to large baseline hazard differences. Importantly, absolute risk reduction, either crude or adjusted, can be calculated from multiplicative survival models. We advocate for a wider use of the absolute scale, especially using additive hazard models, to assess treatment effect and treatment effect modification. PMID:27045168

  17. High frequency effects of modifications to Morison`s equation on the response of a TLP

    SciTech Connect

    Mekha, B.B.; Johnson, C.P.; Roesset, J.M

    1995-12-31

    The work described in this paper is part of a research project conducted at the University of Texas at Austin in conjunction with the Offshore Technology Research Center. The research studies the contribution of different nonlinearities to the global response of tension leg platforms. A rigid body model with three degrees of freedom is selected to represent a TLP hull which consists of four columns and four pontoons. The tendons are modelled as elastic springs allowing for the variation of the axial forces and the effect of setdown. The forces are computed using Morison`s equation with and without the nonlinear modifications formulated by Rainey. Forces on the bottom of a truncated cylinder are employed to account for the diffraction and radiation effects. The effects of these modifications on the high frequency response and on the tendon forces are discussed for different aspects ratios of column diameter to wavelength. Among other conclusions, the tendons forces are dominated by the heave response at the wave frequencies and by the pitch response at the pitch natural frequency.

  18. A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects

    PubMed Central

    Bramsen, Jesper B.; Pakula, Malgorzata M.; Hansen, Thomas B.; Bus, Claus; Langkjær, Niels; Odadzic, Dalibor; Smicius, Romualdas; Wengel, Suzy L.; Chattopadhyaya, Jyoti; Engels, Joachim W.; Herdewijn, Piet; Wengel, Jesper; Kjems, Jørgen

    2010-01-01

    Small interfering RNAs (siRNAs) are now established as the preferred tool to inhibit gene function in mammalian cells yet trigger unintended gene silencing due to their inherent miRNA-like behavior. Such off-target effects are primarily mediated by the sequence-specific interaction between the siRNA seed regions (position 2–8 of either siRNA strand counting from the 5′-end) and complementary sequences in the 3′UTR of (off-) targets. It was previously shown that chemical modification of siRNAs can reduce off-targeting but only very few modifications have been tested leaving more to be identified. Here we developed a luciferase reporter-based assay suitable to monitor siRNA off-targeting in a high throughput manner using stable cell lines. We investigated the impact of chemically modifying single nucleotide positions within the siRNA seed on siRNA function and off-targeting using 10 different types of chemical modifications, three different target sequences and three siRNA concentrations. We found several differently modified siRNAs to exercise reduced off-targeting yet incorporation of the strongly destabilizing unlocked nucleic acid (UNA) modification into position 7 of the siRNA most potently reduced off-targeting for all tested sequences. Notably, such position-specific destabilization of siRNA–target interactions did not significantly reduce siRNA potency and is therefore well suited for future siRNA designs especially for applications in vivo where siRNA concentrations, expectedly, will be low. PMID:20453030

  19. 78 FR 20137 - Probable Economic Effect of Certain Modifications to the North American Free Trade Agreement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-03

    ... list of modifications in the attachment to the March 11, 2013, letter in the form of a correlation... modifications, and the clarifying correlation table are available on the Commission's Web site at...

  20. Modification effects of coping on post-traumatic morbidity among earthquake rescuers.

    PubMed

    Chang, Chia-Ming; Lee, Li-Ching; Connor, Kathryn M; Davidson, Jonathan R T; Lai, Te-Jen

    2008-03-15

    This study aims to investigate the modification effects of coping strategies on the relationships between rescue effort and psychiatric morbidity (i.e. general psychiatric morbidity and post-traumatic morbidity) in earthquake rescue workers. Firefighters (n=193) who were involved in the rescue effort after the Taiwan Chi-Chi earthquake were invited to complete a questionnaire which contained questions on demographics, exposure to rescue work, general psychiatric morbidity, post-traumatic morbidity, and coping strategies. Multivariate regression models with interaction terms were carried out to investigate the modification effect of coping strategies on the relationships between rescue effort and psychiatric morbidities. Older age and longer job experiences (>3 years) were associated with both general psychiatric and post-traumatic morbidities. Coping strategies such as confrontive coping, distancing, seeking social support, accepting responsibility, escape-avoidance, planful problem solving, and positive appraisal significantly modified the effect of exposure to dead bodies on general psychiatric morbidity. Furthermore, confrontive coping, distancing, and planned problem solving significantly modified the effect of exposure to direct rescue involvement on general psychiatric morbidity. However, coping strategies were not observed to buffer the effect of rescue involvement or contact with dead bodies on post-traumatic morbidity. More frequent use of coping strategies could reduce the effect that exposure to rescue efforts has on the incidence of general psychiatric morbidity in rescue workers. However, coping strategies do not seem to reduce the influence of such exposure on trauma-related morbidities. This suggests that coping strategies can be used to prevent general psychiatric morbidity but not trauma-related morbidities. PMID:18258306

  1. Synergistic Effects of Alloying and Thiolate Modification in Furfural Hydrogenation over Cu-Based Catalysts.

    PubMed

    Pang, Simon H; Love, Nicole E; Medlin, J Will

    2014-12-01

    Control of bimetallic surface composition and surface modification with self-assembled monolayers (SAMs) represent two methods for modifying catalyst activity and selectivity. However, possible synergistic effects of employing these strategies in concert have not been previously explored. We investigated the effects of modifying Cu/Al2O3 catalysts by alloying with Ni and modifying with octadecanethiol (C18) SAMs, using furfural hydrogenation as a probe reaction. Incorporation of small amounts of Ni (Cu4Ni) improved catalytic activity while slightly reducing hydrogenation selectivity. Further incorporation of Ni resulted in high rates for decarbonylation and ring-opening. Modification of the Cu4Ni catalyst with C18-SAMs resulted in improvement in both the activity and hydrogenation selectivity. X-ray photoelectron spectroscopy experiments on bimetallic thin films and density functional theory calculations revealed that the C18-SAM kinetically stabilized Cu at the surface under hydrogenation conditions. These results indicate that thiolate monolayers can be used to control surface bimetallic composition to improve catalytic performance. PMID:26278941

  2. Anti-Zeno-effect recovery and Lamb-shift modification in modified vacuum

    SciTech Connect

    Wang Dawei; Wang Ligang; Li Zhenghong; Zhu Shiyao

    2009-10-15

    The influence of the modification of the free vacuum on the quantum Zeno and anti-Zeno effects, as well as the Lamb (energy) shift of a multilevel atom, is studied. A unitary transformation method has been used to include the counter-rotating terms and to obtain the ground state of the whole Hamiltonian. The anti-Zeno effect is recovered if the modified density of states (DOS) has a dip near the transition frequency. The modification of DOS by a dip or a peak will change the Lamb shift compared with that in the free vacuum. Together with our unitary transformation method, there are three different methods to obtain the change in the Lamb shift. Using our method we investigate the change in the Lamb shift and obtain a formula for the change, which is the same as obtained with the method of Louisell [Quantum Statistical Properties of Radiation (Wiley, New York, 1973)] but different from the method of Cohen-Tannoudji et al. [Atom-Photon Interactions: Basic Processes and Applications (Wiley, New York, 1992), pp. 317 and 417]. The correctness of the Lamb shift formulas obtained by the three methods can be easily testified experimentally.

  3. Effects of oxidative modification on gel properties of isolated porcine myofibrillar protein by peroxyl radicals.

    PubMed

    Zhou, Feibai; Zhao, Mouming; Zhao, Haifeng; Sun, Weizheng; Cui, Chun

    2014-04-01

    AAPH-derived (2,2'-azobis (2-amidinopropane) dihydrochloride) peroxyl radicals were selected as representative free radicals of lipid peroxidation to investigate the effects of oxidative modifications on isolated porcine myofibrillar protein structures as well as their rheological and gelling properties. Incubation of myofibrillar protein with increasing concentrations of AAPH resulted in a gradual increase (p<0.05) in carbonyl content and SH→S-S conversion. Results from SDS-PAGE indicated that medium (~1 mM) and relatively high (>3 mM) concentrations of AAPH induced aggregation of myosin and denaturation of myosin, troponin and tropomyosin, respectively. These structural changes resulted in changes on gelation of myofibrillar protein. Low level protein oxidation (AAPH≤0.5 mM) had no remarkable effect (p>0.05) on the viscoelastic pattern of myofibrillar protein gelation. Moderate oxidative modification (AAPH~1mM) enhanced the water-holding capacity (WHC) and texture properties of gels, while further oxidation (AAPH>3mM) significantly reduced the gel quality. PMID:24406430

  4. Effects of modifications to the space shuttle entry guidance and control systems

    NASA Technical Reports Server (NTRS)

    Powell, R. W.; Stone, H. W.; Rowell, L. F.

    1976-01-01

    A nonlinear six degree of freedom entry simulation study was conducted to identify space shuttle guidance and control system software modifications which reduce the control system sensitivity to the guidance system sampling frequency. Several modifications which eliminated the control system sensitivity and associated control limit cycling were examined. The result of the modifications was a reduction in required reaction control system fuel.

  5. Effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains

    PubMed Central

    Tang, Yilin; Han, Sha; Asakawa, Tetsuya; Luo, Yunhe; Han, Xiang; Xiao, Baoguo; Dong, Qiang; Wang, Liang

    2016-01-01

    The past decade has resulted in an increase in the knowledge of molecular mechanisms underlying brain injury induced by intracerebral hemorrhage (ICH). Recent advances have provided a link between epigenetic modification and the regulation of gene expression. 5-hydroxymethylcytosine (5hmC) converted from 5-methylcytosine by the ten-eleven translocation (TET) family of proteins has emerged as a new epigenetic modification. While the dynamics of 5hmC during cerebral ischemia have recently been reported, whether 5hmC is involved in ICH remains unexplored. In this study, we investigated the effects of ICH on DNA hydroxymethylation. We showed that the global level of 5hmC rapidly decreased as early as 24 hours after ICH and persisted until 72 hours. Furthermore, the level of 5hmC in the CpG-rich regions of Akt2, Pdpk1 and Vegf genes was significantly decreased with a minimum level observed at 48 hours or 72 hours. Decreased 5hmC was observed in parallel with an increase in 5-methylcytosine over this time course, and mRNA levels of Akt2, Pdpk1 and Vegf were downregulated upon ICH injury. Finally, Tet1, Tet2 and Tet3 mRNA levels were dramatically decreased in the ICH brain. Our study for the first time established the correlation between DNA hydroxymethylation and ICH injury. Further investigations should examine whether 5hmC modification could be a therapeutic target for the treatment of ICH injury. PMID:27042073

  6. Blue-Violet Laser Modification of Titania Treated Titanium: Antibacterial and Osteo-Inductive Effects

    PubMed Central

    Kawano, Takanori; Prananingrum, Widyasri; Ishida, Yuichi; Goto, Takaharu; Naito, Yoshihito; Watanabe, Megumi; Tomotake, Yoritoki; Ichikawa, Tetsuo

    2013-01-01

    Background Many studies on surface modifications of titanium have been performed in an attempt to accelerate osseointegration. Recently, anatase titanium dioxide has been found to act as a photocatalyst that expresses antibiotic properties and exhibits hydrophilicity after ultraviolet exposure. A blue-violet semiconductor laser (BV-LD) has been developed as near-ultraviolet light. The purpose of this study was to investigate the effects of exposure to this BV-LD on surface modifications of titanium with the goal of enhancing osteoconductive and antibacterial properties. Methods The surfaces of pure commercial titanium were polished with #800 waterproof polishing papers and were treated with anatase titania solution. Specimens were exposed using BV-LD (λ = 405 nm) or an ultraviolet light-emitting diode (UV-LED, λ = 365 nm) at 6 mW/cm2 for 3 h. The surface modification was evaluated physically and biologically using the following parameters or tests: surface roughness, surface temperature during exposure, X-ray diffraction (XRD) analysis, contact angle, methylene blue degradation tests, adherence of Porphyromonas gingivalis, osteoblast and fibroblast proliferation, and histological examination after implantation in rats. Results No significant changes were found in the surface roughness or XRD profiles after exposure. BV-LD exposure did not raise the surface temperature of titanium. The contact angle was significantly decreased, and methylene blue was significantly degraded. The number of attached P. gingivalis organisms was significantly reduced after BV-LD exposure compared to that in the no exposure group. New bone was observed around exposed specimens in the histological evaluation, and both the bone-to-specimen contact ratio and the new bone area increased significantly in exposed groups. Conclusions This study suggested that exposure of titanium to BV-LD can enhance the osteoconductivity of the titanium surface and induce antibacterial properties, similar to

  7. Resistive Memory for Harsh Electronics: Immunity to Surface Effect and High Corrosion Resistance via Surface Modification

    PubMed Central

    Huang, Teng-Han; Yang, Po-Kang; Lien, Der-Hsien; Kang, Chen-Fang; Tsai, Meng-Lin; Chueh, Yu-Lun; He, Jr-Hau

    2014-01-01

    The tolerance/resistance of the electronic devices to extremely harsh environments is of supreme interest. Surface effects and chemical corrosion adversely affect stability and operation uniformity of metal oxide resistive memories. To achieve the surrounding-independent behavior, the surface modification is introduced into the ZnO memristors via incorporating fluorine to replace the oxygen sites. F-Zn bonds is formed to prevent oxygen chemisorption and ZnO dissolution upon corrosive atmospheric exposure, which effectively improves switching characteristics against harmful surroundings. In addition, the fluorine doping stabilizes the cycling endurance and narrows the distribution of switching parameters. The outcomes provide valuable insights for future nonvolatile memory developments in harsh electronics. PMID:24638086

  8. Brownian dynamics simulation of the effect of histone modification on nucleosome structure

    NASA Astrophysics Data System (ADS)

    Li, Wei; Dou, Shuo-Xing; Xie, Ping; Wang, Peng-Ye

    2007-05-01

    Using Brownian dynamics we simulate the effect of histone modification, such as phosphorylation, acetylation, and methylation, on nucleosome structure by varying the interaction force between DNA and the histone octamer. The simulation shows that the structural stability of nucleosome is very sensitive to the interaction force, and the DNA unwrapping from the modified histone octamer usually occurs turn by turn. Furthermore, the effects of temperature and DNA break as well as the competition between modified and normal histone octamers are investigated, with the simulation results being in agreement with the experimental observation that phosphorylated nucleosomes near DNA breaks are more easily depleted. Though the simulation study may only give a coarse grained view of the DNA unwrapping process for the modified histone octamer, it may provide insight into the mechanism of DNA repair.

  9. Estimation of mutagenic effect and modifications of mitosis by silver nanoparticles.

    PubMed

    Prokhorova, I M; Kibrik, B S; Pavlov, A V; Pesnya, D S

    2013-12-01

    We analyzed mutagenic and mitosis-modifying effects of silver nanoparticles (Allium test). Chromosome aberrations and laggings and micronuclei were simultaneously registered in the same sample. Mitotic and phase indexes were calculated. No mutagenic effects were detected after treatment with silver nanoparticles in doses of 1.0, 2.5, 5.0, and 50 mg/liter. Silver nanoparticles in a concentration of 50 mg/liter significantly increased the mitotic index. Nanoparticles in a dose of 5 mg/liter induced slight, but significant increase in mitotic index, but did not affect the ratio of phase indexes. Exposure to silver nanoparticles in concentrations of 1.0 and 2.5 mg/liter was not followed by modification of mitosis. PMID:24319763

  10. Effect modification in the temperature extremes by mortality subgroups among the tropical cities of the Philippines

    PubMed Central

    Seposo, Xerxes T.; Dang, Tran Ngoc; Honda, Yasushi

    2016-01-01

    Background Temperature–mortality relationships have been extensively probed with varying temperature range but with relatively similar patterns and in some instances are being modified by specific mortality groups such as causes of mortality, sex, and age. Objective This study aimed to determine the risk attributions in the extreme temperatures and also identified the risks associated with the various mortality subgroups. Design We used the 2006–2010 daily average meteorological and daily mortality variables from the Philippine Atmospheric Geophysical and Astronomical Services Administration and Philippine Statistics Authority–National Statistics Office, respectively. Mortality data were divided according to cause (cardiovascular and respiratory), sex, and age (0–14 years, 15–64 years, and >64 years). We performed a two-stage analysis to estimate the extreme temperature effects stratified by the different mortality subgroups to observe the effect modification. Results In the pooled analysis, greater risks were observed in the extreme high temperature (99th temperature percentile; RR (relative risk)=2.48 CI: 1.55–3.98) compared to the extreme low temperature (1st temperature percentile; RR=1.23 CI: 0.88–1.72). Furthermore, effect modification by mortality subgroups was evident, especially higher risks for extreme temperatures with respiratory-related diseases, women, and elderly. Conclusions Both sex and age were found to effect modify the risks in extreme temperatures of tropical cities; hence, health-related policies should take these risk variations into consideration to create strategies with respect to the risk population. PMID:27357073

  11. Magnetic zenith effect in the ionospheric modification by an X-mode HF heater wave

    NASA Astrophysics Data System (ADS)

    Blagoveshchenskaya, N. F.; Borisova, T. D.; Haggstrom, I.; Rietveld, M. T.; Yeoman, T. K.

    2013-12-01

    We report experimental results aimed at an investigation of the magnetic zenith effect in the high latitude ionosphere F region from ionospheric modification by powerful HF heater wave with X-polarization. The ionospheric modification was produced by the HF heating facility at Tromsø (Norway) using the phased array with a narrow beam with of 6 degrees. Effective radiated power was varied between 450 and 1000 MW. The HF pump wave radiated in different directions relative to the magnetic field from 90 degrees (vertical) to 78 degrees (magnetic zenith) at frequencies near or above the ordinary-mode critical frequency. The response of the ionosphere plasma to the HF pump wave impact was checked by the UHF incoherent scatter radar located in the immediate vicinity of the HF heater. UHF radar was probing the plasma parameters, such as electron density and temperature (Ne and Te), HF-induced plasma and ion lines in the altitude range from 90 to 600 km. It was running in a scanning mode when UHF radar look angles were changed from 74 to 90 degrees by 1 or 2 degree step. It was clearly demonstrated that the strongest heater-induced effects took place in the magnetic field-aligned direction when HF pointing was also to the magnetic zenith. It was found that strong Ne enhancement of up to 80 % along magnetic field (artificial density ducts) were excited only under HF pumping towards magnetic zenith. The width of the artificial ducts comes to only 2 degrees. The Ne increases were accompanied by the Te enhancements of up to about 50 %. Less pronounced Te increases were also observed in the directions of 84 and 90 degrees. Strong Ne enhancements can be accompanied by excitation of strong HF-induced plasma and ion lines. Thus experimental results obtained points to the strong magnetic zenith effect due to self-focusing powerful HF radio wave with X-mode polarization.

  12. Effect of Plasma Processing and Organosilane Modifications of Polyethylene on Aeromonas hydrophila Biofilm Formation

    PubMed Central

    2014-01-01

    The aim of our research was to study how the modifications of polyethylene—a material commonly used in medicine and water industry—influence bacterial cell attachment and biofilm formation. The native surface was activated and modified using two-step process consisting in the activation of native surface with a H2O vapor plasma followed by its treatment with various organosilanes, namely, [3(tertbutylamine-2hydroxy) propyloxypropyl] diethoxymethylsilane, 1H,1H,2H,2H-perfluorooctylmethyldimethoxysilane, dimethoxydimethylsilane, and isobutylmethyldimethoxysilane. The effect of polyethylene modification after chemical treatment was analyzed using surface tension measurement. The adhesive properties of Aeromonas hydrophila LOCK0968 were studied in water with a low concentration of organic compounds, using luminometric and microscopic methods, and the viability of the adhered bacterial cells was evaluated using the colony forming units method. After two-week incubation the chemically modified materials exhibited better antiadhesive and antibacterial characteristics in comparison to the native surface. Among the examined modifying agents, dimethoxydimethylsilane showed the best desired properties. PMID:24605323

  13. Effect of plasma processing and organosilane modifications of polyethylene on Aeromonas hydrophila biofilm formation.

    PubMed

    Kregiel, Dorota; Niedzielska, Kamila

    2014-01-01

    The aim of our research was to study how the modifications of polyethylene--a material commonly used in medicine and water industry--influence bacterial cell attachment and biofilm formation. The native surface was activated and modified using two-step process consisting in the activation of native surface with a H2O vapor plasma followed by its treatment with various organosilanes, namely, [3(tertbutylamine-2hydroxy) propyloxypropyl] diethoxymethylsilane, 1H,1H,2H,2H-perfluorooctylmethyldimethoxysilane, dimethoxydimethylsilane, and isobutylmethyldimethoxysilane. The effect of polyethylene modification after chemical treatment was analyzed using surface tension measurement. The adhesive properties of Aeromonas hydrophila LOCK0968 were studied in water with a low concentration of organic compounds, using luminometric and microscopic methods, and the viability of the adhered bacterial cells was evaluated using the colony forming units method. After two-week incubation the chemically modified materials exhibited better antiadhesive and antibacterial characteristics in comparison to the native surface. Among the examined modifying agents, dimethoxydimethylsilane showed the best desired properties. PMID:24605323

  14. Effect of mycotoxin-containing diets on epigenetic modifications of mouse oocytes by fluorescence microscopy analysis.

    PubMed

    Zhu, Cheng-Cheng; Hou, Yan-Jun; Han, Jun; Liu, Hong-Lin; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2014-08-01

    Mycotoxins, such as aflatoxin (AF), fumonisin B1, zearalenone (ZEA), and deoxynivalenol (DON), are commonly found in many food commodities. Mycotoxins have been shown to increase DNA methylation levels in a human intestinal cell line. We previously showed that the developmental competence of oocytes was affected in mice that had been fed a mycotoxin-containing diet. In this study, we explored possible mechanisms of low mouse oocyte developmental competence after mycotoxin treatment in an epigenetic modification perspective. Mycotoxin-contaminated maize (DON at 3,875 μg/kg, ZEA at 1,897 μg/kg, and AF at 806 μg/kg) was included in diets at three different doses (mass percentage: 0, 15, and 30%) and fed to mice for 4 weeks. The fluorescence intensity analysis showed that the general DNA methylation levels increased in oocytes from high dose mycotoxin-fed mice. Mouse oocyte histone methylation was also altered. H3K9me3 and H4K20me3 level increased in oocytes from mycotoxin-fed mice, whereas H3K27me3 and H4K20me2 level decreased in oocytes from mycotoxin-fed mice. Thus, our results indicate that naturally occurring mycotoxins have effects on epigenetic modifications in mouse oocytes, which may be one of the reasons for reduced oocyte developmental competence. PMID:24810297

  15. Effect of carbon surface modification with dimethylamine on reactive adsorption of NO(x).

    PubMed

    Deliyanni, Eleni; Bandosz, Teresa J

    2011-03-01

    The wood-based activated carbon, either as received or oxidized with nitric acid, was exposed to dimethylamine vapors. This modification was expected to introduce nitrogen groups. Then, the modified samples were used as adsorbents of NO(2) under dynamic conditions. Both NO(2) breakthrough curves and the NO concentration curves were recorded. The samples before and after exposure to NO(2) were characterized using adsorption of nitrogen, elemental analysis, potentiometric titration, FTIR, and thermal analysis. Modifications with amines resulted in an increase in NO(2) adsorption and in a decrease in NO emission. The effects were more visible when oxidation was used as a pretreatment of the carbon surface. This process increased the incorporation of nitrogen to the carbon matrix via acid-based reactions resulting in the formation of amides and amine carboxylic salts. Besides this, dimethylamine was strongly adsorbed on the carbon surface via hydrogen bonding with oxygen-containing groups. When the samples were exposed to nitrogen dioxide, there was an indication that nitramine and nitrosoamine were formed in the reactions of NO(2) with either amides or amines. In the reactions of amines with NO, nitrosoamines are the likely products. As a next step, the surface of the carbon matrix is reoxidized by NO(2), which is accompanied by the release of NO. PMID:21188988

  16. Does attention redirection contribute to the effectiveness of attention bias modification on social anxiety?

    PubMed

    Yao, Nisha; Yu, Hongyu; Qian, Mingyi; Li, Songwei

    2015-12-01

    Attention bias modification (ABM) is designed to modify threat-related attention bias and thus alleviate anxiety. The current research examined whether consistently directing attention towards targeted goals per se contributes to ABM efficacy. We randomly assigned 68 non-clinical college students with elevated social anxiety to non-valence-specific attend-to-geometrics (AGC), attention modification (AMC), or attention control (ACC) conditions. We assessed subjective, behavioral, and physiological reactivity to a speech task and self-reported social anxiety symptoms. After training, participants in the AMC exhibited an attention avoidance from threat, and those in the AGC responded more rapidly toward targeted geometrics. There was a significant pre- to post-reduction in subjective speech distress across groups, but behavioral and physiological reactivity to speech, as well as self-report social anxiety symptoms, remained unchanged. These results lead to questions concerning effectiveness of ABM training for reducing social anxiety. Further examination of the current ABM protocol is required. PMID:26426451

  17. Smoking during pregnancy and offspring externalizing problems: An exploration of genetic and environmental confounds

    PubMed Central

    D’Onofrio, Brian M.; Van Hulle, Carol A.; Waldman, Irwin D.; Rodgers, Joseph Lee; Harden, K. Paige; Rathouz, Paul J.; Lahey, Benjamin B.

    2013-01-01

    Previous studies have documented that smoking during pregnancy (SDP) is associated with offspring externalizing problems, even when measured covariates were used to control for possible confounds. However, the association may be due to non-measured environmental and genetic factors that increase risk for offspring externalizing problems. The current project used the National Longitudinal Survey of Youth and their children, ages 4–10 years, to explore the relations between SDP and offspring conduct problems (CP), oppositional-defiant problems (ODP), and attention deficit hyperactivity problems (ADHP) using methodological and statistical controls for confounds. When offspring were compared to their own siblings who differed in their exposure to prenatal nicotine, there was no effect of SDP on offspring CP and ODP. This suggests that SDP does not have a causal effect on offspring CP and ODP. There was a small association between SDP and ADHP, consistent with a causal effect of SDP, but the magnitude of the association was greatly reduced by methodological and statistical controls. Genetically informed analyses suggest that unmeasured environmental variables influencing both SDP and offspring externalizing behaviors account for the previously observed associations. That is, the current analyses imply that important unidentified environmental factors account for the association between SDP and offspring externalizing problems, not teratogenic effects of SDP. PMID:18211732

  18. Water dispersible upconverting nanoparticles: effects of surface modification on their luminescence and colloidal stability

    NASA Astrophysics Data System (ADS)

    Wilhelm, Stefan; Kaiser, Martin; Würth, Christian; Heiland, Josef; Carrillo-Carrion, Carolina; Muhr, Verena; Wolfbeis, Otto S.; Parak, Wolfgang J.; Resch-Genger, Ute; Hirsch, Thomas

    2015-01-01

    We present a systematic study on the effect of surface ligands on the luminescence properties and colloidal stability of β-NaYF4:Yb3+,Er3+ upconversion nanoparticles (UCNPs), comparing nine different surface coatings to render these UCNPs water-dispersible and bioconjugatable. A prerequisite for this study was a large-scale synthetic method that yields ~2 g per batch of monodisperse oleate-capped UCNPs providing identical core particles. These ~23 nm sized UCNPs display an upconversion quantum yield of ~0.35% when dispersed in cyclohexane and excited with a power density of 150 W cm-2, underlining their high quality. A comparison of the colloidal stability and luminescence properties of these UCNPs, subsequently surface modified with ligand exchange or encapsulation protocols, revealed that the ratio of the green (545 nm) and red (658 nm) emission bands determined at a constant excitation power density clearly depends on the surface chemistry. Modifications relying on the deposition of additional (amphiphilic) layer coatings, where the initial oleate coating is retained, show reduced non-radiative quenching by water as compared to UCNPs that are rendered water-dispersible via ligand exchange. Moreover, we could demonstrate that the brightness of the upconversion luminescence of the UCNPs is strongly affected by the type of surface modification, i.e., ligand exchange or encapsulation, yet hardly by the chemical nature of the ligand.We present a systematic study on the effect of surface ligands on the luminescence properties and colloidal stability of β-NaYF4:Yb3+,Er3+ upconversion nanoparticles (UCNPs), comparing nine different surface coatings to render these UCNPs water-dispersible and bioconjugatable. A prerequisite for this study was a large-scale synthetic method that yields ~2 g per batch of monodisperse oleate-capped UCNPs providing identical core particles. These ~23 nm sized UCNPs display an upconversion quantum yield of ~0.35% when dispersed in

  19. Daily temperature and mortality: a study of distributed lag non-linear effect and effect modification in Guangzhou

    PubMed Central

    2012-01-01

    Background Although many studies have documented health effects of ambient temperature, little evidence is available in subtropical or tropical regions, and effect modifiers remain uncertain. We examined the effects of daily mean temperature on mortality and effect modification in the subtropical city of Guangzhou, China. Methods A Poisson regression model combined with distributed lag non-linear model was applied to assess the non-linear and lag patterns of the association between daily mean temperature and mortality from 2003 to 2007 in Guangzhou. The case-only approach was used to determine whether the effect of temperature was modified by individual characteristics, including sex, age, educational attainment and occupation class. Results Hot effect was immediate and limited to the first 5 days, with an overall increase of 15.46% (95% confidence interval: 10.05% to 20.87%) in mortality risk comparing the 99th and the 90th percentile temperature. Cold effect persisted for approximately 12 days, with a 20.39% (11.78% to 29.01%) increase in risk comparing the first and the 10th percentile temperature. The effects were especially remarkable for cardiovascular and respiratory mortality. The effects of both hot and cold temperatures were greater among the elderly. Females suffered more from hot-associated mortality than males. We also found significant effect modification by educational attainment and occupation class. Conclusions There are significant mortality effects of hot and cold temperatures in Guangzhou. The elderly, females and subjects with low socioeconomic status have been identified as especially vulnerable to the effect of ambient temperatures. PMID:22974173

  20. [VLP vaccines and effects of HIV-1 Env protein modifications on their antigenic properties].

    PubMed

    Vzorov, A N; Compans, R W

    2016-01-01

    An ideal protective HIV-1 vaccine can elicit broadly neutralizing antibodies, capable of preventing HIV transmission. The strategies of designing vaccines include generation of soluble recombinant proteins which mimic the native Env complex and are able to enhance the immunogenicity of gp120. Recent data indicate that the cytoplasmic tail (CT) of the Env protein has multiple functions, which can affect the early steps of infection, as well as viral assembly and antigenic properties. Modifications in the CT can be used to induce conformational changes in functional regions of gp120 and to stabilize the trimeric structure, avoiding immune misdirection and induction of non-neutralizing antibody responses. Env-trimers with modified CTs in virus-like particles (VLPs) are able to induce antibodies with broad spectrum neutralizing activity and high avidity and have the potential for developing an effective vaccine against HIV. PMID:27414779

  1. The Effect of Structural Modifications on Ionic Conductivity in Newly-Designed Polyester Electrolytes

    NASA Astrophysics Data System (ADS)

    Pesko, Danielle; Jung, Yuki; Coates, Geoff; Balsara, Nitash

    2015-03-01

    Gaining a fundamental understanding of the relationship between molecular structure and ionic conductivity of polymer electrolytes is an essential step toward designing next generation materials for battery applications. In this study, we use a systematic set of newly-designed polyesters with varying side-chain lengths and oxygen functional groups to elucidate the effects of structural modifications on the conductive properties of the corresponding electrolytes. Mixtures of polyesters and lithium bis(trifluromethanesulfonyl)imide (LiTFSI) were characterized using ac impedance spectroscopy to measure the ionic conductivity at various temperatures and salt concentrations. The relative conductivities of these electrolytes in the dilute limit are directly comparable to results of molecular dynamics simulations performed using the same polymers. The simulations correspond well with the experimental results, and provide molecular level insight about the solvation environment of the lithium ions and how the ions transport through these polyesters.

  2. Modification of β-Sheet Forming Peptide Hydrophobic Face: Effect on Self-Assembly and Gelation

    PubMed Central

    2016-01-01

    β-Sheet forming peptides have attracted significant interest for the design of hydrogels for biomedical applications. One of the main challenges is the control and understanding of the correlations between peptide molecular structure, the morphology, and topology of the fiber and network formed as well as the macroscopic properties of the hydrogel obtained. In this work, we have investigated the effect that functionalizing these peptides through their hydrophobic face has on their self-assembly and gelation. Our results show that the modification of the hydrophobic face results in a partial loss of the extended β-sheet conformation of the peptide and a significant change in fiber morphology from straight to kinked. As a consequence, the ability of these fibers to associate along their length and form large bundles is reduced. These structural changes (fiber structure and network topology) significantly affect the mechanical properties of the hydrogels (shear modulus and elasticity). PMID:27089379

  3. Modification of β-Sheet Forming Peptide Hydrophobic Face: Effect on Self-Assembly and Gelation.

    PubMed

    Elsawy, Mohamed A; Smith, Andrew M; Hodson, Nigel; Squires, Adam; Miller, Aline F; Saiani, Alberto

    2016-05-17

    β-Sheet forming peptides have attracted significant interest for the design of hydrogels for biomedical applications. One of the main challenges is the control and understanding of the correlations between peptide molecular structure, the morphology, and topology of the fiber and network formed as well as the macroscopic properties of the hydrogel obtained. In this work, we have investigated the effect that functionalizing these peptides through their hydrophobic face has on their self-assembly and gelation. Our results show that the modification of the hydrophobic face results in a partial loss of the extended β-sheet conformation of the peptide and a significant change in fiber morphology from straight to kinked. As a consequence, the ability of these fibers to associate along their length and form large bundles is reduced. These structural changes (fiber structure and network topology) significantly affect the mechanical properties of the hydrogels (shear modulus and elasticity). PMID:27089379

  4. Effectiveness of a volunteer-delivered lifestyle modification program for reducing cardiovascular disease risk factors.

    PubMed

    Rankin, Paul; Morton, Darren P; Diehl, Hans; Gobble, John; Morey, Peter; Chang, Esther

    2012-01-01

    Lifestyle modification has been demonstrated to effectively reduce the risk factors associated with cardiovascular disease, but there is a perception that it is costly to administer and resource. The present study examined the results achieved by a 30-day lifestyle modification program (Coronary Health Improvement Project) delivered by volunteers in a community setting. Changes in selected biometric measures of 5,070 participants in the Coronary Health Improvement Project programs delivered throughout North America (January 2006 to October 2009), were assessed. Overall, significant reductions (p < 0.001) were recorded in body mass (-3.2%), systolic and diastolic blood pressure (-4.9% and -5.3%, respectively), total cholesterol (-11.0%), low-density lipoprotein cholesterol (-13.0%), triglycerides (-7.7%), and fasting plasma glucose (-6.1%). Stratification of the data revealed more dramatic responses in those presenting with the greatest risk factor levels. Those presenting with cholesterol levels >280 mg/dl recorded an average reduction of 19.8%. A mean decrease of 16.1% in low-density lipoprotein levels was observed among those who entered the program with a low-density lipoprotein level >190 mg/dl. Individuals who presented with triglycerides >500 mg/dl recorded a mean reduction of 44.1%. The Framingham assessment forecast that approximately 70 cardiac events would be averted during the subsequent decade in the cohort because of the program. In conclusion, significant reductions in cardiovascular disease risk factors can be achieved in a 30-day lifestyle intervention delivered by volunteers, providing a cost-effective mode of administering lifestyle medicine. PMID:21944675

  5. Effect of surface modification and UVA photoactivation on antibacterial bioactivity of zinc oxide powder

    NASA Astrophysics Data System (ADS)

    Ann, Ling Chuo; Mahmud, Shahrom; Bakhori, Siti Khadijah Mohd; Sirelkhatim, Amna; Mohamad, Dasmawati; Hasan, Habsah; Seeni, Azman; Rahman, Rosliza Abdul

    2014-02-01

    The effects of surface modification of zinc oxide (ZnO) powder and UVA illumination on the powder towards Escherichia coli and Staphylococcus aureus were investigated. FESEM-EDS results showed that oxygen annealing increased the O:Zn ratio on the surface of ZnO-rod and ZnO-plate samples. Surface conductances of ZnO-rod and ZnO-plate pellets were reduced from 1.05 nS to 0.15 nS and 1.34 nS to 0.23 nS, respectively. Meanwhile, UVA illumination on the surface of the ZnO-rod and ZnO-plate samples was found to improve surface conductance to 7.08 nS and 6.51 nS, respectively, due to the release of charge carrier. Photoluminescence results revealed that oxygen annealing halved the UV emission intensity and green emission intensity, presumably caused by oxygen absorption in the ZnO lattice. The antibacterial results showed that oxygen-treated ZnO exhibited slightly higher growth inhibition on E. coli and S. aureus compared with unannealed ZnO. UVA illumination on ZnO causes the greatest inhibition toward E. coli and S. aureus. Under the UVA excitation, the inhibition of E. coli increased by 18% (ZnO-rod) and 13% (ZnO-plate) while the inhibition of S. aureus increased by 22% (ZnO-rod) and 21% (ZnO-plate). Release of reactive oxygen species were proposed in antibacterial mechanisms, which were aided by surface modification and UVA photoactivation. The reactive oxygen species disrupted the DNA and protein synthesis of the bacterial cell, causing bacteriostatic effects toward E. coli and S. aureus.

  6. Tribocorrosion studies of metallic biomaterials: The effect of plasma nitriding and DLC surface modifications.

    PubMed

    Zhao, Guo-Hua; Aune, Ragnhild E; Espallargas, Nuria

    2016-10-01

    The medical grade pure titanium, stainless steel and CoCrMo alloy have been utilized as biomaterials for load-bearing orthopedic prosthesis. The conventional surgery metals suffer from a combined effect of wear and corrosion once they are implanted, which may significantly accelerate the material degradation process. In this work, the tribocorrosion performance of the metallic biomaterials with different surface modifications was studied in the simulated body fluid for the purpose of investigating the effect of the surface treatments on the tribocorrosion performance and eventually finding the most suitable implantation materials. The metals were subjected to surface modifications by plasma nitriding in different treatment temperatures or physical vapor deposition (PVD) to produce diamond-like carbon (DLC) coating, respectively. The dry wear and tribocorrosion properties of the samples were evaluated by using a reciprocating ball-on-disc tribometer equipped with an electrochemical cell. Prior to the tribocorrosion tests, their electrochemical behavior was measured by the potentiodynamic polarization in phosphate buffer saline (PBS) solution at room temperature. Both stainless steel and CoCrMo after low temperature nitriding kept their passive nature by forming an expanded austenite phase. The DLC coated samples presented the low anodic corrosion current due to the chemical inertness of the carbon layer. During the tribocorrosion tests at open circuit potential, the untreated and low temperature nitrided samples exhibited significant potential drop towards the cathodic direction, which was a result of the worn out of the passive film. Galvanic coupling was established between the depassivated (worn) area and the still passive (unworn) area, making the materials suffered from wear-accelerated corrosion. The DLC coating performed as a solid lubricant in both dry wear and tribocorrosion tests, and the resulting wear after the tests was almost negligible. PMID:27348147

  7. Impacts of temperature change on ambulance dispatches and seasonal effect modification

    NASA Astrophysics Data System (ADS)

    Cheng, Jian; Xu, Zhiwei; Zhao, Desheng; Xie, Mingyu; Yang, Huihui; Wen, Liying; Li, Kesheng; Su, Hong

    2016-05-01

    Ambulance dispatch is a proxy of acute health outcomes, and growing epidemiological evidence documented its relation to extreme temperature events. Research, however, on short-term temperature change and ambulance dispatches is scarce. We aimed to investigate the effect of short-term temperature change on ambulance dispatches and potential modification by season. Daily data on ambulance dispatch and weather factors were collected in Huainan, a Chinese inland city from December 2011 through December 2013. A Poison generalized linear regression model combined with distributed lag nonlinear model was constructed to examine the association of temperature change between neighboring days (TCN) with ambulance dispatches. The effect modification by season was also examined. There were 48,700 ambulance attendances during the study period. A statistically significant association of TCN with ambulance dispatches was observed. Temperature rise between neighboring days (TCN > 0) was associated with elevated adverse risk of ambulance dispatches, and the effects appeared to be acute (lag0, on the current day) and could last for at least a week, while temperature drop between neighboring days (TCN < 0) had a protective effect. For a 1 °C increase of TCN at lag0 and lag06 (on the 7-day moving average), the risk of ambulance dispatches increased by 2 % (95 % CI 1-3 %) and 7 (95 % CI 1-13 %), respectively. Extreme TCN increase (95th percentile, 3.3 °C vs. 0 °C) at lag0 and lag05 was accompanied by 6 (95 % CI 3-8 %) and 27 % (95 % CI 12-44 %) increase in ambulance dispatches. Ambulance dispatches were more vulnerable to extremely great temperature rise in summer and autumn. TCN was adopted for the first time to quantify the impact of short-term temperature change on ambulance dispatches. Temperature drop between neighboring days (TCN < 0) had a protective effect on ambulance dispatches, while temperature rise between neighboring days (TCN > 0) could acutely trigger the increase in

  8. The effects of size and surface modification of amorphous silica particles on biodistribution and liver metabolism in mice

    NASA Astrophysics Data System (ADS)

    Lu, Xiaoyan; Ji, Cai; Jin, Tingting; Fan, Xiaohui

    2015-05-01

    Engineered nanoparticles, with unconventional properties, are promising platforms for biomedical applications. Since they may interact with a wide variety of biomolecules, it is critical to understand the impact of the physicochemical properties of engineered nanoparticles on biological systems. In this study, the effects of particle size and surface modification alone or in combination of amorphous silica particles (SPs) on biological responses were determined using a suite of general toxicological assessments and metabonomics analysis in mice model. Our results suggested that amino or carboxyl surface modification mitigated the liver toxicity of plain-surface SPs. 30 nm SPs with amino surface modification were found to be the most toxic SPs among all the surface-modified SP treatments at the same dosage. When treatment dose was increased, submicro-sized SPs with amino or carboxyl surface modification also induced liver toxicity. Biodistribution studies suggested that 70 nm SPs were mainly accumulated in liver and spleen regardless of surface modifications. Interestingly, these two organs exhibited different uptake trends. Furthermore, metabonomics studies indicated that surface modification plays a more dominant role to affect the liver metabolism than particle size.

  9. Hamilton study: distribution of factors confounding the relationship between air quality and respiratory health

    SciTech Connect

    Pengelly, L.D.; Kerigan, A.T.; Goldsmith, C.H.; Inman, E.M.

    1984-10-01

    Hamilton, Ontario is an industrial city with a population of 300,000 which is situated at the western end of Lake Ontario. Canada's two largest iron and steel mills are located here; the city historically has had relatively poor air quality, which has improved markedly in the last 25 years. Concern about the health effects of current air quality recently led us to carry out an epidemiological study of the effects of air pollution on the respiratory health of over 3500 school children. Respiratory health was measured by pulmonary function testing of each child, and by an assessment of each child's respiratory symptoms via a questionnaire administered to the parents. Previous studies had shown that other environmental factors (e.g. parental smoking, parental cough, socioeconomic level, housing, and gas cooking) might also affect respiratory health, and thus confound any potential relationships between health and air pollution. The questionnaire also collected information on many of these confounding factors. For the purposes of initial analysis, the city was divided into five areas in which differences in air quality were expected. In general, factors which have been associated with poor respiratory health were observed to be more prevalent in areas of poorer air quality.

  10. Hydroimidazolone Modification of Human αA-Crystallin: Effect on the Chaperone Function and Protein Refolding Ability

    PubMed Central

    Gangadhariah, Mahesha H.; Wang, Benlian; Linetsky, Mikhail; Henning, Christian; Spanneberg, Robert; Glomb, Marcus A.; Nagaraj, Ram H.

    2010-01-01

    Alpha A-crystallin is a molecular chaperone; it prevents aggregation of denaturing proteins. We have previously demonstrated that upon modification by a metabolic α-dicarbonyl compound, methylglyoxal (MGO), αA-crystallin becomes a better chaperone. Alpha A-crystallin also assists in refolding of denatured proteins. Here, we have investigated the effect of mild modification of αA-crystallin by MGO (with 20-500 μM) on the chaperone function and its ability to refold denatured proteins. Under the conditions used, mildly modified protein contained mostly hydroimidazolone modifications. The modified protein exhibited an increase in chaperone function against thermal aggregation of βL- and γ-crystallins, citrate synthase (CS), malate dehydrogenase (MDH) and lactate dehydrogenase (LDH) and chemical aggregation of insulin. The ability of the protein to assist in refolding of chemically denatured βL- and γ-crystallins, MDH and LDH, and to prevent thermal inactivation of CS were unchanged after mild modification by MGO. Prior binding of catalytically inactive, thermally denatured MDH or the hydrophobic probe, 2-p-toluidonaphthalene-6-sulfonate (TNS) abolished the ability of αA-crystallin to assist in the refolding of denatured MDH. However, MGO-modification of chaperone-null TNS-bound αA-crystallin resulted in partial regain of the chaperone function. Taken together, these results demonstrate that: 1) hydroimidazolone modifications are sufficient to enhance the chaperone function of αA-crystallin but such modifications do not change its ability to assist in refolding of denatured proteins, 2) the sites on the αA-crystallin responsible for the chaperone function and refolding are the same in the native αA-crystallin and 3) additional hydrophobic sites exposed upon MGO modification, which are responsible for the enhanced chaperone function, do not enhance αA-crystallin's ability to refold denatured proteins. PMID:20085807

  11. Confounding Impacts of Iron Reduction on Arsenic Retention

    SciTech Connect

    Tufano, K.J.; Fendorf, S.

    2009-05-26

    A transition from oxidizing to reducing conditions has long been implicated to increase aqueous As concentrations, for which reductive dissolution of iron (hydr)oxides is commonly implicated as the primary culprit. Confounding our understanding of processes controlling As retention, however, is that reductive transformation of ferrihydrite has recently been shown to promote As retention rather than release. To resolve the role iron phases have in regulating arsenic concentrations, here we examine As desorption from ferrihydrite-coated sands presorbed with As(lll); experiments were performed at circumneutral pH under Fe-reducing conditions with the dissimilatory iron reducing bacterium Shewanella putrefaciens strain CN-32 over extended time periods. We reveal that with the initial phase of iron reduction, ferrihydrite undergoes transformation to secondary phases and increases As(lll) retention (relative to abiotic controls). However, with increased reaction time, cessation of the phase transitions and ensuing reductive dissolution result in prolonged release of As(III) to the aqueous phase. Our results suggest that As(lll) retention during iron reduction is temporally dependent on secondary precipitation of iron phases; during transformation to secondary phases, particularly magnetite, As(lll) retention is enhanced even relative to oxidized systems. However, conditions that retard secondary transformation (more stable iron oxides or limited iron reducing bacterial activity), or prolonged anaerobiosis, will lead to both the dissolution of ferric (hydr)oxides and release of As(lll) to the aqueous phase.

  12. Post-translational modification of osteopontin: Effects on in vitro hydroxyapatite formation and growth

    SciTech Connect

    Boskey, Adele L.; Christensen, Brian; Taleb, Hayat; Sorensen, Esben S.

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Thrombin-cleaved fragments of milk-osteopontin effect hydroxyapatite formation differently. Black-Right-Pointing-Pointer N- and C-terminal fragments promoted hydroxyapatite formation and growth. Black-Right-Pointing-Pointer A central fragment inhibited hydroxyapatite formation and growth. Black-Right-Pointing-Pointer Binding to collagen or hydroxyapatite seed crystals modified these effects. -- Abstract: The manuscript tests the hypothesis that posttranslational modification of the SIBLING family of proteins in general and osteopontin in particular modify the abilities of these proteins to regulate in vitro hydroxyapatite (HA) formation. Osteopontin has diverse effects on hydroxyapatite (HA) mineral crystallite formation and growth depending on the extent of phosphorylation. We hypothesized that different regions of full-length OPN would also have distinct effects on the mineralization process. Thrombin fragmentation of milk OPN (mOPN) was used to test this hypothesis. Three fragments were tested in a de novo HA formation assay; an N-terminal fragment (aa 1-147), a central fragment (aa 148-204) denoted SKK-fragment and a C-terminal fragment (aa 205-262). Compared to intact mOPN the C- and N-terminal fragments behaved comparably, promoting HA formation and growth, but the central SKK-fragment acted as a mineralization inhibitor. In a seeded growth experiment all fragments inhibited mineral proliferation, but the SKK-fragment was the most effective inhibitor. These effects, seen in HA-formation and seeded growth assays in a gelatin gel system and in a pH-stat experiment were lost when the protein or fragments were dephosphorylated. Effects of the fully phosphorylated protein and fragments were also altered in the presence of fibrillar collagen. The diverse effects can be explained in terms of the intrinsically disordered nature of OPN and its fragments which enable them to interact with their multiple partners.

  13. Are We Missing Something Pertinent? A Bias Analysis of Unmeasured Confounding in the Firearm-Suicide Literature.

    PubMed

    Miller, M; Swanson, S A; Azrael, D

    2016-01-01

    Despite the magnitude and consistency of risk estimates in the peer-reviewed literature linking firearm availability and suicide, inferring causality has been questioned on the theoretical basis that existing studies may have failed to account for the possibility that members of households with firearms differ from members of households without firearms in important ways related to suicide risk. The current bias analysis directly addresses this concern by describing the salient characteristics that such an unmeasured confounder would need to possess in order to yield the associations between firearm availability and suicide observed in the literature when, in fact, the causal effect is null. Four US studies, published between 1992 and 2003, met our eligibility criteria. We find that any such unmeasured confounder would need to possess an untenable combination of characteristics, such as being not only 1) as potent a suicide risk factor as the psychiatric disorders most tightly linked to suicide (e.g., major depressive and substance use disorders) but also 2) an order of magnitude more imbalanced across households with versus without firearms than is any known risk factor. No such confounder has been found or even suggested. The current study strongly suggests that unmeasured confounding alone is unlikely to explain the association between firearms and suicide. PMID:26769723

  14. Surface modification and laser pulse length effects on internal energy transfer in DIOS.

    PubMed

    Luo, Guanghong; Chen, Yong; Siuzdak, Gary; Vertes, Akos

    2005-12-29

    Benzyl-substituted benzylpyridinium (BP) chloride salts were used as a source of thermometer ions to probe the internal energy (IE) transfer in desorption/ionization on porous silicon (DIOS). To modify their wetting properties and the interaction energies with the thermometer ions, the DIOS surfaces were silylated to produce trimethylsilyl- (TMS), amine- (NH2), perfluoroalkyl- (PFA), and perfluorophenyl-derivatized (PFP) surfaces. Two laser sources--a nitrogen laser with pulse length of 4 ns and a mode locked 3 x omega Nd:YAG laser with a pulse length of 22 ps--were utilized to induce desorption/ionization and fragmentation at various laser fluence levels. The corresponding survival yields were determined as indicators of the IE transfer and the IE distributions were extracted. In most cases, with increasing the laser fluence in a broad range (approximately 20 mJ/cm2), no change in IE transfer was observed. For ns excitation, this was in remarkable contrast with MALDI, where increasing the laser fluence resulted in sharply (within approximately 5 mJ/cm2) declining survival yields. Derivatization of the porous silicon surface did not affect the survival yields significantly but had a discernible effect on the threshold fluence for ion production. The IE distributions determined for DIOS and MALDI from alpha-cyano-4-hydroxycinnamic acid reveal that the mean IE value is always lower for the latter. Using the ps laser, the IE distribution is always narrower for DIOS, whereas for ns laser excitation the width depends on surface modification. Most of the differences between MALDI and DIOS described here are compatible with the different dimensionality of the plume expansion and the differences in the activation energy of desorption due to surface modifications. PMID:16375447

  15. Incorporating linked healthcare claims to improve confounding control in a study of in-hospital medication use

    PubMed Central

    Franklin, Jessica M; Eddings, Wesley; Schneeweiss, Sebastian; Rassen, Jeremy A

    2015-01-01

    Introduction The Premier Perspective hospital billing database provides a promising data source for studies of inpatient medication use. However, in-hospital recording of confounders is limited, and incorporating linked healthcare claims data available for a subset of the cohort may improve confounding control. We investigated methods capable of adjusting for confounders measured in a subset, including complete case analysis, multiple imputation of missing data, and propensity score (PS) calibration. Methods Methods were implemented in an example study of adults in Premier undergoing percutaneous coronary intervention (PCI) in 2004-2008 and exposed to either bivalirudin or heparin. In a subset of patients enrolled in UnitedHealth for at least 90 days before hospitalization, additional confounders were assessed from healthcare claims, including comorbidities, prior medication use, and service use intensity. Diagnostics for each method were evaluated, and methods were compared with respect to the estimates and confidence intervals of treatment effects on repeat PCI, bleeding, and in-hospital death. Results Of 210,268 patients in the hospital-based cohort, 3,240 (1.5%) had linked healthcare claims. This subset was younger and healthier than the overall study population. The linked subset was too small for complete case evaluation of 2 of the 3 outcomes of interest. Multiple imputation and PS calibration did not meaningfully impact treatment effect estimates and associated confidence intervals. Conclusions Despite more than 98% missingness on 24 variables, PS calibration and multiple imputation incorporated confounders from healthcare claims without major increases in estimate uncertainty. Additional research is needed to determine the relative bias of these methods. PMID:25935198

  16. Effects of laser fluence on silicon modification by four-beam laser interference

    SciTech Connect

    Zhao, Le; Li, Dayou; Wang, Zuobin Yue, Yong; Zhang, Jinjin; Yu, Miao; Li, Siwei

    2015-12-21

    This paper discusses the effects of laser fluence on silicon modification by four-beam laser interference. In this work, four-beam laser interference was used to pattern single crystal silicon wafers for the fabrication of surface structures, and the number of laser pulses was applied to the process in air. By controlling the parameters of laser irradiation, different shapes of silicon structures were fabricated. The results were obtained with the single laser fluence of 354 mJ/cm{sup 2}, 495 mJ/cm{sup 2}, and 637 mJ/cm{sup 2}, the pulse repetition rate of 10 Hz, the laser exposure pulses of 30, 100, and 300, the laser wavelength of 1064 nm, and the pulse duration of 7–9 ns. The effects of the heat transfer and the radiation of laser interference plasma on silicon wafer surfaces were investigated. The equations of heat flow and radiation effects of laser plasma of interfering patterns in a four-beam laser interference distribution were proposed to describe their impacts on silicon wafer surfaces. The experimental results have shown that the laser fluence has to be properly selected for the fabrication of well-defined surface structures in a four-beam laser interference process. Laser interference patterns can directly fabricate different shape structures for their corresponding applications.

  17. Effects of electrode surface modification with chlorotoxin on patterning single glioma cells.

    PubMed

    Asphahani, Fareid; Zheng, Xiaohao; Veiseh, Omid; Thein, Myo; Xu, Jian; Ohuchi, Fumio; Zhang, Miqin

    2011-05-21

    A microchip patterned with arrays of single cancer cells can be an effective platform for the study of tumor biology, medical diagnostics, and drug screening. However, patterning and retaining viable single cancer cells on defined sites of the microarray can be challenging. In this study we used a tumor cell-specific peptide, chlorotoxin (CTX), to mediate glioma cell adhesion on arrays of gold microelectrodes and investigated the effects of three surface modification schemes for conjugation of CTX to the microelectrodes on single cell patterning, which include physical adsorption, covalent bonding mediated by N-hydroxysuccinimide (NHS), and covalent bonding via crosslinking succinimidyl iodoacetate and Traut's (SIA-Traut) reagents. The CTX immobilization to microelectrodes was confirmed by high-resolution X-ray photoelectron spectroscopy. Physically adsorbed CTX showed better support for cell adhesion and is more effective in confining adhered cells on the electrodes than covalently-bound CTX. Furthermore, cell adhesion and spreading on microelectrodes were quantified in real-time by impedance measurements, which revealed an impedance signal from physically adsorbed CTX electrodes four times greater than the signal from covalently-bound CTX electrodes. PMID:21678586

  18. Study of the modifications needed for effective operation NASTRAN on IBM virtual storage computers

    NASA Technical Reports Server (NTRS)

    Mccormick, C. W.; Render, K. H.

    1975-01-01

    The necessary modifications were determined to make NASTRAN operational under virtual storage operating systems (VS1 and VS2). Suggested changes are presented which will make NASTRAN operate more efficiently under these systems. Estimates of the cost and time involved in design, coding, and implementation of all suggested modifications are included.

  19. Effect of Timbre and Register Modifications of Musical Stimuli on Young Children's Identification of Chord Changes.

    ERIC Educational Resources Information Center

    Costa-Giomi, Eugenia

    1994-01-01

    Reviews research related to children's musical development. Reports on a study of 125 kindergarten and first-grade students on the impact of modification of timbre and register of musical stimuli. Finds that timbre modification helped children recognize chord changes with first graders identifying more changes than did kindergartners. (CFR)

  20. The assessment of cortisol in human hair: associations with sociodemographic variables and potential confounders.

    PubMed

    Dettenborn, L; Tietze, A; Kirschbaum, C; Stalder, T

    2012-11-01

    To inform the future use of hair cortisol measurement, we have investigated influences of potential confounding variables (natural hair colour, frequency of hair washes, age, sex, oral contraceptive (OC) use and smoking status) on hair cortisol levels. The main study sample comprised 360 participants (172 women) covering a wide range of ages (1-91 years; mean = 25.95). In addition, to more closely examine influences of natural hair colour and young age on hair cortisol levels, two additional samples comprising 69 participants with natural blond or dark brown hair (hair colour sample) as well as 28 young children and 34 adults (young age sample) were recruited. Results revealed a lack of an effect for natural hair colour, OC use, and smoking status on hair cortisol levels (all p's >0.10). No influence of frequency of hair washes was seen for proximal hair segments (p = 0.335) but for the third hair segment indicating lower cortisol content (p = 0.008). We found elevated hair cortisol levels in young children and older adults (p < 0.001). Finally, men showed higher hair cortisol levels than women (p = 0.002). The present data indicate that hair cortisol measurement provides a useful tool in stress-related psychobiological research when applied with the consideration of possible confounders including age and sex. PMID:22356099

  1. Child welfare clients have higher risks for teenage childbirths: which are the major confounders?

    PubMed Central

    Vinnerljung, Bo; Hjern, Anders

    2016-01-01

    Background: Aiming to support effective social intervention strategies targeting high-risk groups for teenage motherhood, this study examined to what extent the elevated crude risks of teenage childbirth among child welfare groups were attributable to the uneven distribution of adverse individual and family background factors. Methods: Comprehensive longitudinal register data for more than 700 000 Swedish females born 1973–1989 (including around 29 000 child welfare clients) were analysed by means of binary logistic regression. The Karlson/Holm/Breen-method was used to decompose each confounding factor’s relative contribution to the difference between crude and adjusted odds ratios (ORs). Results: Elevated crude risks for teenage childbirth are to a large extent attributable to selection on observables. Girls’ school failure was the most potent confounder, accounting for 28–35% of the difference between crude and adjusted ORs. Conclusion: As in majority populations, girls’ school failure was a strong risk factor for teenage childbirth among former child welfare children. At least among pre-adolescents, promoting school performance among children in the child welfare system seems to be a viable intervention path. PMID:27085195

  2. Review of methods for handling confounding by cluster and informative cluster size in clustered data

    PubMed Central

    Seaman, Shaun; Pavlou, Menelaos; Copas, Andrew

    2014-01-01

    Clustered data are common in medical research. Typically, one is interested in a regression model for the association between an outcome and covariates. Two complications that can arise when analysing clustered data are informative cluster size (ICS) and confounding by cluster (CBC). ICS and CBC mean that the outcome of a member given its covariates is associated with, respectively, the number of members in the cluster and the covariate values of other members in the cluster. Standard generalised linear mixed models for cluster-specific inference and standard generalised estimating equations for population-average inference assume, in general, the absence of ICS and CBC. Modifications of these approaches have been proposed to account for CBC or ICS. This article is a review of these methods. We express their assumptions in a common format, thus providing greater clarity about the assumptions that methods proposed for handling CBC make about ICS and vice versa, and about when different methods can be used in practice. We report relative efficiencies of methods where available, describe how methods are related, identify a previously unreported equivalence between two key methods, and propose some simple additional methods. Unnecessarily using a method that allows for ICS/CBC has an efficiency cost when ICS and CBC are absent. We review tools for identifying ICS/CBC. A strategy for analysis when CBC and ICS are suspected is demonstrated by examining the association between socio-economic deprivation and preterm neonatal death in Scotland. PMID:25087978

  3. Confounding variables in the environmental toxicology of arsenic.

    PubMed

    Gebel, T

    2000-04-01

    Arsenic is one of the most important global environmental toxicants. For example, in regions of West Bengal and Inner Mongolia, more than 100000 persons are chronically exposed to well water often strongly contaminated with As. Unfortunately, a toxicologically safe risk assessment and standard setting, especially for long-term and low-dose exposures to arsenic, is not possible. One reason is that the key mechanism of arsenic's tumorigenicity still is not elucidated. Experimental data indicate that either DNA repair inhibition or DNA methylation status alteration may be causal explanations. Moreover, when comparing epidemiological data, it cannot be ruled out that the susceptibility to arsenic's carcinogenicity may be different between Mexican and Taiwanese people. Some other studies indicate that some Andean populations do not develop skin cancer after long-term exposure to As. It is not known yet how this resistance could be mediated. Finally, the situation is even more complicated when taking into consideration that there are several compounds suspected to modulate the chronic environmental toxicity of arsenic, variables that may either enhance or suppress the in vivo genotoxicity and carcinogenicity of the metalloid. Among them are nutritional factors like selenium and zinc as well as drinking water co-contaminants like antimony. Further, yet unidentified factors influencing the body burden and/or the excretion of arsenic are possibly prevailing: preliminary data from own human biomonitoring studies showed a peaking of As in urine samples of non-exposed people which was not caused by elevated exposure to As through seafood consumption. The relevance of these putative confounding variables cannot be finally evaluated yet. Further experimental as well as epidemiological studies are needed to answer these questions. This would help to conduct a toxicologically improved risk assessment, especially for low-dose and long-term exposures to arsenic. PMID:10781883

  4. Evaluating the Cost-Effectiveness of Lifestyle Modification versus Metformin Therapy for the Prevention of Diabetes in Singapore

    PubMed Central

    Png, May Ee; Yoong, Joanne Su-Yin

    2014-01-01

    Background In Singapore, as diabetes is an increasingly important public health issue, the cost-effectiveness of pursuing lifestyle modification programs and/or alternative prevention strategies is of critical importance for policymakers. While the US Diabetes Prevention Program (DPP) compared weight loss through lifestyle modification with oral treatment of diabetes drug metformin to prevent/delay the onset of type 2 diabetes in pre-diabetic subjects, no data on either the actual or potential cost effectiveness of such a program is available for East or South-east Asian populations. This study estimates the 3-year cost-effectiveness of lifestyle modification and metformin among pre-diabetic subjects from a Singapore health system and societal perspective. Methodology Cost effectiveness was analysed from 2010–2012 using a decision-based model to estimate the rates of getting diabetes, healthcare costs and health-related quality of life. Cost per quality-adjusted life year (QALY) was estimated using costs relevant to the time horizon of the study from Singapore. All costs are expressed in 2012 US dollars. Principal Findings The total economic cost for non-diabetic subjects from the societal perspective was US$25,867, US$28,108 and US$26,177 for placebo, lifestyle modification and metformin intervention respectively. For diabetic patients, the total economic cost from the societal perspective was US$32,921, US$35,163 and US$33,232 for placebo, lifestyle modification and metformin intervention respectively. Lifestyle modification relative to placebo is likely to be associated with an incremental cost per QALY gained at US$36,663 while that of metformin intervention is likely to be US$6,367 from a societal perspective. Conclusion Based on adaptation of the DPP data to local conditions, both lifestyle modification and metformin intervention are likely to be cost-effective and worth implementing in Singapore to prevent or delay the onset of type 2 diabetes. However

  5. Effect of lycopene and {beta}-carotene on peroxynitrite-mediated cellular modifications

    SciTech Connect

    Muzandu, Kaampwe; Ishizuka, Mayumi; Sakamoto, Kentaro Q.; Shaban, Zein; El Bohi, Khlood; Kazusaka, Akio; Fujita, Shoichi . E-mail: fujita@vetmed.hokudai.ac.jp

    2006-09-15

    Peroxynitrite formed by the reaction of superoxide and nitric oxide is a highly reactive species with a role in various pathological processes such as cancer, chronic inflammation, and cardiovascular and neurological diseases. In the present study, the effect of the carotenoids, lycopene and {beta}-carotene, on peroxynitrite-mediated modifications in plasmid DNA as well as cellular DNA and proteins were investigated. In pUC18 plasmid DNA, these carotenoids strongly inhibited DNA strand breaks caused by peroxynitrite generated from 3-morpholinosydnonimine (SIN-1). SIN-1 was also used to determine effects on DNA damage and protein tyrosine nitration in Chinese hamster lung fibroblasts. SIN-1 dose-dependently increased nitration of proteins in cells above basal levels as determined by Western blotting. This nitration was inhibited in the presence of the uric acid as well as lycopene. Physiological concentrations (0.31-10 {mu}M) of lycopene and {beta}-carotene also had protective effects on DNA damage, as measured by the comet assay. Lycopene significantly reduced DNA damage particularly, in the median range of concentrations (2.5 {mu}M). The protective effects of lycopene and {beta}-carotene could be due to their scavenging of reactive oxygen (ROS) and/or nitrogen species (RNS) as they reduce the amount of intracellular ROS/RNS produced following treatment with SIN-1 by as much as 47.5% and 42.4%, respectively. The results obtained in this study suggest that carotenoids may alleviate some of the deleterious effects of peroxynitrite and possibly other reactive nitrogen species as well in vivo.

  6. Adverse health effects due to arsenic exposure: Modification by dietary supplementation of jaggery in mice

    SciTech Connect

    Singh, Nrashant; Kumar, D.; Lal, Kewal; Raisuddin, S.; Sahu, Anand P.

    2010-02-01

    Populations of villages of eastern India and Bangladesh and many other parts of the world are exposed to arsenic mainly through drinking water. Due to non-availability of safe drinking water they are compelled to depend on arsenic-contaminated water. Generally, poverty level is high in those areas and situation is compounded by the lack of proper nutrition. The hypothesis that the deleterious health effects of arsenic can be prevented by modification of dietary factors with the availability of an affordable and indigenous functional food jaggery (sugarcane juice) has been tested in the present study. Jaggery contains polyphenols, vitamin C, carotene and other biologically active components. Arsenic as sodium-m-arsenite at low (0.05 ppm) and high (5 ppm) doses was orally administered to Swiss male albino mice, alone and in combination with jaggery feeding (250 mg/mice), consecutively for 180 days. The serum levels of total antioxidant, glutathione peroxidase and glutathione reductase were substantially reduced in arsenic-exposed groups, while supplementation of jaggery enhanced their levels in combined treatment groups. The serum levels of interleukin-1beta, interleukin-6 and TNF-alpha were significantly increased in arsenic-exposed groups, while in the arsenic-exposed and jaggery supplemented groups their levels were normal. The comet assay in bone marrow cells showed the genotoxic effects of arsenic, whereas combination with jaggery feeding lessened the DNA damage. Histopathologically, the lung of arsenic-exposed mice showed the necrosis and degenerative changes in bronchiolar epithelium with emphysema and thickening of alveolar septa which was effectively antagonized by jaggery feeding. These results demonstrate that jaggery, a natural functional food, effectively antagonizes many of the adverse effects of arsenic.

  7. Effects of surface modification of talc on mechanical properties of polypropylene/talc composites

    NASA Astrophysics Data System (ADS)

    Liu, Keyan; Stadlbauer, Wolfgang; Zitzenbacher, Gernot; Paulik, Christian; Burgstaller, Christoph

    2016-03-01

    Low compatibility of polymer matrix and dispersed filler negatively affects the performance of polymeric composites. In order to improve the adhesion between the components in a compound the polymer matrix or/and the filler particles should be modified with a compatibilizer or/and a coupling agent. An overview of our current research on the effect of the addition of silane treated and untreated talc powders on the mechanical properties of polypropylene/talc composites is presented in this paper. Different silane coupling agents (3-aminopropyltriethoxysilane, 3-glycidoxypropyltrimethoxysilane and 3-methacryloxypropyltrimethoxysilane) were used to improve the adhesion at the surface of talc powders. Maleic anhydride grafted polypropylene was utilized to increase the adhesion between the polypropylene matrix and talc powders. The content of maleic anhydride grafted polypropylene (MA-g-PP) was varied between 1 and 5 wt% in polypropylene/talc composites. The surface modification of talc powders has a significant effect on the interfacial structure and the mechanical properties such as tensile strength and impact strength of polypropylene/talc composites. The experiments show that polypropylene grafted with maleic anhydride together with silane surface treatment exhibits the highest potential for improvements in this field.

  8. Flaperon Modification Effect on Jet-Flap Interaction Noise Reduction for Chevron Nozzles

    NASA Technical Reports Server (NTRS)

    Thomas, Russell H.; Mengle, Vinod G.; Stoker, Robert W.; Brusniak, Leon; Elkoby, Ronen

    2007-01-01

    Jet-flap interaction (JFI) noise can become an important component of far field noise when a flap is immersed in the engine propulsive stream or is in its entrained region, as in approach conditions for under-the-wing engine configurations. We experimentally study the effect of modifying the flaperon, which is a high speed aileron between the inboard and outboard flaps, at both approach and take-off conditions using scaled models in a free jet. The flaperon modifications were of two types: sawtooth trailing edge and mini vortex generators (vg s). Parametric variations of these two concepts were tested with a round coaxial nozzle and an advanced chevron nozzle, with azimuthally varying fan chevrons, using both far field microphone arrays and phased microphone arrays for source diagnostics purposes. In general, the phased array results corroborated the far field results in the upstream quadrant pointing to JFI near the flaperon trailing edge as the origin of the far field noise changes. Specific sawtooth trailing edges in conjunction with the round nozzle gave marginal reduction in JFI noise at approach, and parallel co-rotating mini-vg s were somewhat more beneficial over a wider range of angles, but both concepts were noisier at take-off conditions. These two concepts had generally an adverse JFI effect when used in conjunction with the advanced chevron nozzle at both approach and take-off conditions.

  9. Effects of channel modifications on the hydrology of Chicod Creek basin, North Carolina, 1975-87

    USGS Publications Warehouse

    Mason, R.R., Jr.; Simmons, C.E.; Watkins, S.A.

    1990-01-01

    Drainage modifications in this Coastal Plain basin from 1978 to 1981 consisted of channel excavation and clearing of blockages. A study was begun in 1975 to define hydrologic conditions of the basin before, during, and after modifications and to determine what changes were attributed to modifications. Surface-water conditions were altered during and following modifications. Minimum flow at Juniper Branch was increased from less than 0.1 cu ft/sec to 0.4 cu ft/second;streamflow variability was reduced from an index of 0.87 to 0.49. In-channel velocity at Chicod Creek was increased from a mean of 0.4 ft/sec to 1.5 ft/sec. Substantial groundwater level declines were observed in wells 180 and 250 ft from Juniper Branch during the modifications phase;these were 0.4 and 0.2 ft, respectively. However, most surface-water and groundwater conditions returned nearly to premodification levels by 1987. Water-quality characteristics monitored during the investigation included physical, chemical, and bacteriological characteristics. Physical characteristics monitored were suspended sediment, temperature, dissolved oxygen, and pH. Of these physical characteristics, only sediment concentrations increased substantially during channel modifications. Chemical characteristics studied were major dissolved constituents, nutrients, trace metals, and pesticides. Substantial changes ranged from a decline in total iron concentrations of 77% to an increase in total nitrite concentrations of 130%. Changes in many chemical characteristics persisted following channel modifications. Bacterial counts did not change substantially.

  10. Structural and physico-chemical properties of insoluble rice bran fiber: effect of acid–base induced modifications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The structural modifications of insoluble rice bran fiber (IRBF) by sequential regimes of sulphuric acid (H2SO4) and their effects on the physicochemical attributes were studied. The increment of H2SO4 concentration resulted in decreased water holding capacity that ultimately enhanced the oil bindin...